The success story of two young children who were the first to receive paediatric bone morrow transplants in the UAE was shared at an event in Abu Dhabi.

Burjeel Medical Citys bone marrow transplant unit, which was inaugurated in the capital in September, carried out the procedures on Jordana, 5, and Ahmed Daoud Al Uqabi, 2, just two weeks apart in April.

Both are now on the road to recovery and act as examples of the life-saving work being performed under a landmark health strategy.

Previously patients in the Emirates requiring bone marrow transplants would have to seek medical treatment abroad.

In the next two years, doctors hope to cut by half the number of patients needing to undergo such transplant procedures.

They spoke of efforts to drive forward the country's health sector at the first Emirates Paediatric Bone Marrow Transplant Congress in Abu Dhabi on Friday.

Jordana's donor for the milestone procedure was her 10-year-old sister Jolina. Photo: Burjeel Medical City

Two-year-old Ahmed Daoud Al Uqabi was the first child with thalassemia, a genetic defect in the composition of haemoglobin, to receive a bone marrow transplant at the Burjeel unit. His donor was an older sibling.

He had travelled to the Emirates from Iraq for treatment, highlighting the UAE's mission to deliver world-class health care and become a centre for medical tourism.

Jordana, 5, from Uganda, who has sickle-cell anaemia, benefited from a matched sibling transplant that involved her receiving healthy stem cells from her sister Jolina, 10.

Her sister attended the Abu Dhabi conference, along with their mother.

The allogeneic stem cell transplant involves transferring healthy blood stem cells from a donor to replace a patients diseased or damaged bone marrow.

The complex procedure requires collecting stem cells from the donor's blood, bone marrow within a donor's hipbone, or from the blood of a donated umbilical cord, before transferring them to the patient.

Dr Zainul Aabideen, head of paediatric haematology and oncology at BMC, said after Jordana's surgery that she had endured great pain and suffering in her life.

Two-year-old Ahmed Daoud Al Uqabi was the first child with thalassemia, a genetic defect in the composition of haemoglobin, to receive a bone marrow transplant at the Burjeel unit. Photo: VPS Healthcare

The only curative option for this life-threatening condition is bone marrow transplantation," Dr Aabideen said.

"Prior to this procedure, there would have been immense suffering for the patient. The entire care team here at the hospital, as well as the childs parents, are delighted that the transplant will remove this pain from her life.

Both Ahmed and Jordana are on the road to recovery and medics have their sights set on helping hundreds more like them.

"Abu Dhabi is currently distinguished by the application of the highest standards used in the treatment of bone marrow transplantation," said Dr Fatima Al Kaabi, director of the Abu Dhabi Bone Marrow Transplant Programme at the Abu Dhabi Stem Cell Centre.

"Providing these distinguished services in the country makes it easier for us as specialists in this field to provide medical care ... in addition to reducing costs compared with treatment abroad.

"We expect, during the next two years, with the presence of bone marrow transplants for children, to reduce requests for treatment abroad for these cases to 50 per cent.

Updated: May 28, 2022, 3:45 AM

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First children in UAE to receive bone marrow transplants bring hope to others - The National

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DirectCell system (Biogennix)

Biogennix has announced that itsDirectCelladvanced bone grafting systemhas now been used in more than 500 cases.

The DirectCell system includes a bone graft product with advanced bone regeneration properties along with novel instrumentation engineered to harvest high concentrations of patient stem cells, say Biogennix.

The cell-stimulating graft within the system is theadvanced synthetic bone graft, Agilon, which is available in a mouldable and strip form. Agilon products are based on Biogennixs TrelCor technologythat contains ananocrystalline hydroxycarbanoapatite graft surfacewhich actively participates in bone regeneration.

The DirectCell system also provides surgeons two methods of collecting bone marrow derived stem cells, either through the harvesting of stem cell aspirate with significantly higher stem cell counts (compared to standard bone marrow aspirate) or marrow-rich autograft dowels.

The DirectCell System provides surgeons the means to harvest tissue with high stem cell counts and combine it with a graft material that is actively involved in the cellular bone formation response, said Mark Borden, Biogennixs CTO. This results in an optimal biological graft that immediately begins the bone regeneration process.

Jeffrey Wang, chief of orthopaedic spine service at USC and co-director of the USC Spine Center (Los Angeles, USA), has been he using the product in his spine fusion cases. He commented: When you combine live cells with an advanced surface, you are optimising the healing response. Surgeons and hospitals alike need innovative solutions with strong scientific backing, which incorporate new biological technologies.

Biogennix CEO Chris MacDuff, added: As a company our strength has always been our focus and deep expertise in advanced bone regeneration technologies. I attribute the swift success of the DirectCell system primarily to the solid science supporting its benefits.

When you use the patients own cells, you completely eliminate the risk of disease transmission that has recently been seen with cadaver-based stem cell products. The DirectCell system not only enables the harvest of significantly higher cell counts, but it is a safer and significantly more cost-effective alternative.

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Biogennix's DirectCell advanced bone grafting system used in 500th case - Spinal News International

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Therunt-related transcription factor 1 (RUNX1) gene is known as a critical regulator of embryogenesis and definitive hematopoiesis in vertebrates, playing a vital role in the generation of hematopoietic stem cells (HSCs) and their differentiation into the myeloid and lymphoid lineage. The discovery of RUNX1 mutationsas the cause of familial platelet disorder (FPD) was pivotal to understanding the implications of this gene in hematological malignancies.FPD is an inherited bone marrow failure syndrome (IBMFS) with quantitative and qualitative platelet abnormalities and a highpredisposition to acute myeloid leukemia (AML)[1,2].IBMFS are genetic disorders characterized by cytopenia and hypoproliferation of one or more cell lineages in the bone marrow[1]. The production of blood cells (erythrocytes, granulocytes, and platelets) is compromised because of the mono-allelic gene mutation in one of certain bone marrow genes. Besides FPD, the other most common IBMFSs include Fanconi anemia (FA), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS), and severe congenital neutropenia (SCN)[3]. Patients with IBMFSs show a predisposition to developinghematological complications, such as myelodysplastic syndrome (MDS) or AML[3]. MDS is a pre-leukemic state defined by the presence of refractory cytopenia or refractory cytopenia with an excess of blasts (5-29%) in the bone marrow. AML is a blood cancer that is characterized by rapid leukemic blast cell growth and the presence of more than 30% myeloid blasts in the bone marrow[2].

Recent studies have shown that RUNX1 germline mutations in patients with IBMFS arelikeacquiredorsomatic RUNX1 mutations that were found in myeloid malignancies, particularly in MDS and AML[3].It has become clear that somatic RUNX1 mutations are more prevalent in MDS/AML that is secondary to IBMFS, such as FA and SCN. Unlike acquired MDS/AML, these forms of secondary MDS/AML are often refractory to treatment,resulting ina poor prognosis. Because the somatic mutation of RUNX1 was first identified in MDS and AML, RUNX1 has become known to be one of the most frequently mutated genes in a variety of hematologicalmalignancies[4].

Despite recent research having demonstrated the strong association of RUNX1 mutations in a variety of hematological malignancies, it is unclear howRUNX1 mutations contributetothepathogenesis of hematological malignancies in IBMFS. What are the frequencies of different RUNX1 mutations in various subgroups of hematological malignancies, as well as their impact on prognosis? Furthermore, is there any potential for the developmentof new cancer therapies following recent findings regarding the role of RUNX1 in the malignanttransformation[5]?

In this article, we summarize new research onthe role of RUNX1 mutations, published in February 2020 by three different groups[6-8].They performed different experiments in human, mouse, and induced pluripotent stem cell (iPSC) models to decipher the role of the RUNX1 gene in the malignant transformation of IBMFS; the mechanisms of pathogenesis; clinical and molecular characteristics of RUNX1 mutations; and the potential for the treatmentof cancers. The mouse and iPSC models suggested that secondary RUNX1 mutations in clones with granulocyte colony-stimulating factor 3 receptor (GCSF3R) mutations are weakly leukemogenic and that an additional clonal mutation in theCXXC finger protein 4 (CXXC4) gene is required for the full transformation to AML[9].Mutations in the CXXC4 gene lead to the hyperproduction of inflammatory proteins called theten-eleven translocation (TET2) proteins.This inflammation, in combination with the RUNX1 mutations, drives the development of myeloid malignancies[10].The other pathogenic mechanisms wherein RUNX1 mutations may initiate tumor cellproliferation 18arethe inhibition of the p53 pathway and hypermethylation of the promoter of Wingless and Int1 (WNT) inhibitor gene called secreted frizzled-related protein 2 (SFRP2)[11,12].

These discoveries may have the potential to aidthe development of new therapeutic strategies.Specifically, immunotherapy may be employed for suppression of the excessive immune response to hyperproduction of TET2 proteins.The other potential therapeutics, such as mouse double minute 2 (MDM2) andpoly adenosine diphosphate-ribose polymerase(PARP) inhibitors, may be used to inhibit the hyperactivation of the p53 pathway or hypersensitivity to DNA damage resulting from RUNX1 mutations[11]. Because the presence of RUNX1 mutation represents a poor prognostic factor in patients with MDS or AML, the investigation of various biomarkers is critical as they may detect the clones with RUNX1 mutation, in the early stages of leukemic progression[7].

Search Strategy

The PubMed online database search was used to select the articles which are included in this review. The findings were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following medical subject heading (MeSH) parameters were used: inherited and bone marrow and failure and syndromes. This search resulted in 5,051 articles.

Selection Criteria

The identified articles were further filtered. Thereview selectedonly articles that met the following criteria: (1) papers published between January and December 2020; (2) free full-text available; (3) papers written in English; and (4) studies conducted on human participants. Among screened articles, only clinical trials, meta-analyses, randomized controlled trials, and systematic reviews were included. Five citations from other sources were not included because they were not relevant to the topic. To further select the articles, we included the following MeSH terms: hematologic neoplasms, gene expression regulation, leukemic, RUNX1 protein, human, and Neutropenia, Severe Congenital, Autosomal recessive. Any articles that were not relevant to the role of the RUNX1 gene were excluded. These criteria allowcomparison between articles; however, it should be noted that differing lab protocols between studies prevents validation of results using the same assessment tool. A systematic search review is reported using the PRISMA 2020 guidelines [13].The diagram is presented in Figure1.

The selected articles were used to evaluate the clinical and molecular characteristics of RUNX1 mutation in various types of hematological malignancies, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies for hematological malignancies with RUNX1 mutations.

Clinical and Molecular Characteristics of RUNX1 Mutation in Hematological Malignancies

RUNX1 gene has multiple biological functions in the human body. It regulates hematopoiesis, the cell cycle and genome stability, the p53 signaling pathway, apoptosis, and ribosomal biogenesis. During hematopoiesis, this gene controls the development of HSCs and their differentiation in different lineages. The transition from the G1-S to the G2/M phase of the cell cycle is facilitated by RUNX1. This gene controls cellular proliferation and differentiation via direct regulation of transcription, achieved by binding promoters of the genes that are encoding ribosomal RNA/proteins. According to recently published data, somatic mutations of RUNX1 were observed in various types of hematological malignancies. We present the frequency of RUNX1 mutations in various types of hematological malignancies in Table 1 below.

Most frequently, somatic mutations of RUNX1 were associated with the development of myeloproliferative neoplasm (MPN) (10.3-37.5%) and chronic myelomonocytic leukemia (CMML) (32.1-37%). Despite this, the association between RUNX1 somatic mutations and MDS was only 10%.

The Mechanisms of Pathogenesis Caused by RUNX1 Mutations

In the selected studies, the different mechanisms of pathogenesis caused by RUNX1 mutations were characterized. It has been shown that loss of RUNX1 function causes inhibition of differentiation of HSCs. Therefore, in pre-leukemia, we found expansion of HSCs and progenitor cells. RUNX1 mutations may attenuate the G1-S phase and enhance the proliferation of hematopoietic cells that occur during the mitotic phase of the cell cycle (G2/M) [7]. The mutations can also result in genomic instability, leading to increased DNA damage and impaired DNA repair. Some mutations in RUNX1 are associated with alterations of signaling pathways, such as WNT and p53. Hypermethylation of the WNT inhibitor gene promoter, SFRP2, can lead to aberrant activation of the WNT signaling pathway and leukemogenesis in AML. When functioning normally, the RUNX1 gene acts to increase transcriptional activity of the p53 signaling pathway, in response to DNA damage caused by exposure to different agents such as chemicals, radiation, and toxins. Mutations in RUNX1 may lead to defects in p53-mediated apoptosis/DNA repair/cell cycle regulation resulting in tumorigenesis. Furthermore, loss-of-function mutations of RUNX1 may aid tumor-initiating cells in hematological malignancies via inhibition of p53 signaling and apoptosis, among other mechanisms. Such mutations have reduced ribosomal biogenesis in HSCs and directed to malignant proliferative processes in the pre-leukemic stage [6]. In vivo studies, administration of amino acid L-leucine to patients with DBA resulted in loss-of-function mutations in ribosomal protein genes. Research into iPSC confirmed that the introduction of the mutated RUNX1 gene into CD34+CD45+ cells via lentivirus can stimulate receptor which binds the granulocyte colony-stimulating factor 3 receptor (GCSF3R) and initiates the production of immature cells. The percentage of immature cells was significantly increased when compared to the percentage in empty vector (ev) control studies. The myeloid differentiation of GCSF3R-d715/RUNX1-D171N and GCSF3R-d715/ev cells without RUNX1-D171N lentiviral expression vector or with an ev is presented in Figure 2.

Potential Therapeutic Strategies for RUNX1-Mutated Cases of Hematological Malignancies

Clinical trials demonstrated potential therapeutic strategies for RUNX1 mutated hematologic malignancies.Based on the current RUNX1 roles in human hematopoiesis, various therapeutic options were developed. Thus far, the different DNA repair inhibitors can be useful in the M phase of cell cycle repair or bypassing the cells with damage because RUNX1 mutations lead to DNA damage and impaired DNA repair[32].In addition, adriamycin as an antineoplastic drug can stimulate the RUNX1-p53 complex which is important in the activation of p53-mediated apoptosis[11].L-leucine can be used to improve anemia in the genetic DBA mouse models and DBA patients. This agent is a potent stimulator of protein translation that is initialized by the activation of the mammalian target of rapamycin (mTOR) protein kinase. This kinase stimulates protein synthesis[33].Another agent, clustered regulatory interspaced short palindromic repeats-associated genes (CRISPR-Cas) can be used as a genomic targeted treatment as this agent can edit the RUNX1 gene by cutting pieces of DNA where RUNX1 mutations are, followed by stimulating natural DNArepair[6].Finally, hypoxia-inducible factor 1 (HIF-1) inhibitor can potentially treat various hematological malignancies as a modulator of cell metabolism. MDS and other hematological malignancies are in hypoxia-like status and produce their energy through the tricarboxylic acid (TCA) cycle. The use of HIF-1 inhibitor can suppress the TCA cycle and modulate it into an aerobic metabolic pathway called glycolysis through which the normal cells are supplied with energy. The recent studies proposed therapeutic strategies that employed the different pathophysiological mechanisms to correct the RUNX1 mutations, as shown in Figure3.

The RUNX1 gene plays essential roles in a wide range of biological processes, including the development of HSCs, cell proliferation,megakaryocyte maturation, T lymphocyte-lineage differentiation,and apoptosis. It is not surprising that RUNX1 dysfunction is associated with the development of IBMFSs and various hematological malignancies[7,21,34].

Previous studies have shown that RUNX1 is one of the most frequently mutated genes in hematologicalmalignancies. RUNX1mutations account for about 10-15% of all somatic mutations that have been detected in MDS[21,35].The incidence of RUNX1 mutations in CMML and chronic myelogenous leukemia (CML) is even higher, ranging from 32.1% to 37%, respectively[36].RUNX1 mutations have also been reported in 14% of patients withMPN,15.6% of patients with acute lymphoblastic leukemia (ALL),and 10.3-37.5% of AML patients. Importantly, these studies have shown that mutated RUNX1can be used as an independent prognostic factor for event-freesurvival (EFS), relapse-free survival (RFS), or overall survival (OS) in hematological malignancies[37].Therefore, AML patients with RUNX1 mutations had worse prognosis, resistance to chemotherapy, and inferior EFS,RFS, and OS. Reduced OS was also observed in high-risk MDS patients with RUNX1mutations who had poor clinical outcomes and shorter latency for progression to secondary AML[38,39].

Little is known about the role of the RUNX1 gene in the development of secondary somatic mutations in patients with IBMFSs and how these mutations lead to hematological malignancies. The data have shown that individuals with IBMFSs, such as FPD and FA, have a high lifetime risk (30-44%) of developing MDS and AML [29,30]. Among FA-associated MDS or MDS/AML patients, RUNX1 mutations were detected in the range from 20.7% to 31.25%, respectively. In SCN-MDS/AML patients RUNX1 mutations were seen at the highest rate of up to 64.5% which revealed that these types of mutations are the most frequent somatic secondary mutations in SCN-MDS/AML [31,40,41]. Given that the patients with SCN are more prone to develop somatic RUNX1 mutations, SCN/AML has been recognized as an important model to further investigate the role of secondary RUNX1 mutations in the molecular pathogenesis of hematological malignancies. SCN is an IBMFS classified by severe neutropenia and life-threatening infections such as fungal infections or bacterial sepsis [40]. The most frequent mutated gene is encoding neutrophil elastase (ELANE). The treatment consists of life-long administration of GCSF3 that successfully alleviates the neutrophil counts [42]. As is common with other forms of IBMFSs, SCN patients have a high risk of developing MDS or AML. The incidence of developing MDS or AML directly correlates to the number of years on GCSF3. Therefore, after 15 years on GCSF3, the incidence of developing MDS or AML is 21% [31]. The majority of SCN patients with leukemic progression develop hematopoietic clones with somatic mutations in GCSF3R, resulting in a truncated form of GCSF3R [42]. It is important to note that these clones can persist for several months or years before MDS or AML becomes symptomatic, raising the question of how these GCSF3R mutants contribute to the malignant transformation of SCN [31,41]. Given this, a mouse model was used to study the role of RUNX1. In this study, a truncated GCSF3R (GCSF3R-D715) identical to the mutant GCSF3R form in SCN patients was expressed in mice [43]. In addition, a lentiviral expression vector was used to express RUNX1-mutant D171N in conjunction with an enhanced green fluorescent protein (eGFP) [8]. The mouse bone marrow (BM) cells with expressed GCSF3R-D715 mutation were subsequently serially transplanted into wild-type recipients. Before transplantation, the recipients were treated either three times per week with GCSF3 or with peripheral blood solvent (PBS) control. Primary recipients who were treated with GCSF3 and transplanted with GCSFR3-RUNX1-mutant BM cells developed myeloblasts in peripheral blood (PB) that were sustained for at least 30 weeks. None of these mice developed symptoms of AML, suggesting that the elevated myeloblasts in the PB reflected a pre-leukemic state rather than a fully transformed state. However, upon transplantation in secondary and tertiary recipients, mice developed GCSF3R-RUNX1-mutant AML. Whole-exome sequencing (WES) was performed on lin-c-kit (LK) cells and revealed that AML cells from the secondary and tertiary recipients had seven-fold higher expressions of CXXC4 mutations than the cells from the primary recipient. Recently, CXXC4 mutations have also been detected in human AML cases [9]. It seems that CXXC4 mutations enhance the production of TET2 protein which is known to be an inflammatory factor and has a similar role to interferon-gamma, interleukin-6, and others. Interferon-gamma and interleukin-6 are cytokines that are produced in response to infections and tissue damage, with pro- and anti-inflammatory effects. Hyperproduction of TET2 leads to inflammatory processes that may play an important role in the development of myeloid malignancy involving RUNX1 mutations [10]. In conclusion, isolated RUNX-Runt homology domain (RHD) mutations are only weakly leukemogenic and an additional clonal mutation that reduces levels of TET2 is what drives the full transformation to AML [8,32]. The data suggest the need for further investigation into the somatic RUNX1 mutations in HSPCs that already harbour a GCSF3R nonsense mutation. To achieve this, a CRISPR/Cas9-based strategy was used to introduce a patient-derived GCSF3R nonsense mutation into iPSC. CRISPR-Cas9 is a technology used for removing, adding, or altering sections of the DNA. After culturing iPSC, CD34+CD45+ cells were transduced using a lentivirus to express the RUNX1-RHD D171N mutant. The experiments confirm that the combinations of GCSF3R and RUNX1 mutations have a moderate effect on myeloid differentiation and result in an increasing number of myeloblasts. These findings corroborate the findings in the mouse model and suggest that secondary RUNX1 mutations in clones with GCSF3R mutations are not sufficient to fully transform to AML.

Most of the RUNX1 mutations are mono-allelic, such as in FPD, an IBMFS resulting in apredisposition to leukemia[1,2]. Germline RUNX1 mutations are dominant-negative mutations and correlate toa higher risk of developing hematological malignancies compared to RUNX1 loss-of-function mutations[5-8].It is important to note, however, that such germline mutations alone are not sufficient for the development of leukemia and additional mutations in RUNX1 (bi-allelicmutations)or epigenetic modifiers, splicing factors, or tumor suppressors are required to induce myeloid malignancies[1,4].

It has been observed that mutations in RUNX1 are associated with alterations of p53 and other signaling pathways, such as WNT, bone morphogenetic proteins (BMP), transforming growth factor-beta (TGF-), rat sarcoma-the extracellular signal-regulated kinase (RAS-ERK), Hippo-yes-1-associated protein (YAP1), and Notch.Unlike mono-allelic mutations, loss-of-function mutations of RUNX1 are responsible for initiating tumor cell proliferation by inhibiting the p53 signaling pathway and apoptosis.Thep53 pathway is activated in DNA damage and is responsible for DNA repair.RUNX1 increases the transcriptional activity of p53, potentially via up-regulation of p300-mediated acetylation of p53. RUNX1 mutations lead to a reduction of p53-mediated apoptosis[11].The WNT pathway is important for cellular proliferation and differentiation, with aberrant activation of this pathway being reported in various tumors. RUNX1 mutations were closely associated with hypermethylation of the promoter of one of the WNT inhibitor genes (SFRP2) in AML. It was suggested that the WNT inhibitor hypermethylation might lead to aberrant activation of the WNT signaling pathway. It is suggested that mutation in the RUNX1 gene can interact with the SFRP2 gene which is known as an inhibitor gene responsible for the suppression of the WNT signaling pathway. Due to interaction with genetic alterations, the hypermethylation of SFRP2 gene promoter is initiated and leads to leukemogenesis where cellular proliferation and differentiation are uncontrolled[12].

This review has highlighted the importance of studying the role of somatic RUNX1 mutations in the pathogenesis of hematological malignancies and the potential implications in the development of oncological therapies. This review does, however, had some limitations.First,the results presented in this review were collected from only three articles that were published over the limited time frame of one year. In addition, we included only articles that were available in the PubMed database and in both free text format and English language. This review did not apply the same assessment tools such as the lab protocols for conducting experiments. Variations between lab protocols did not allow the comparison of study results. In all the articles included, the scope of the study was the role of RUNX1 mutations in animal and human disease models, including only SCN and FA as the IBMFS representatives without knowing if RUNX1 mutations may contribute to the development of malignancies in other IBMFS. A broader literature search and greater inclusion of studies about RUNX1 mutations in pathogenesis in other IBMFS may better represent and validate the inferences from this review.

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A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With...

Bone Marrow Stem Cells Comments Off on A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With… | May 29th, 2022

The new report by Expert Market Research titled, Global Stem Cell Banking Market Report and Forecast 2021-2026, gives an in-depth analysis of the globalstem cell banking market, assessing the market based on its segments like Service type, product type, utilisation, bank type, application, and major regions like Asia Pacific, Europe, North America, Middle East and Africa and Latin America. The report tracks the latest trends in the industry and studies their impact on the overall market. It also assesses the market dynamics, covering the key demand and price indicators, along with analysing the market based on the SWOT and Porters Five Forces models.

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The key highlights of the report include:

Market Overview (2021-2026)

The global stem cell bank market is primarily driven by the advancements in the field of medicine and the rising prevalence of genetic and degenerativediseases. Further, the increasing research and development of more effective technologies for better preservation, processing, and storage of stem cells are aiding the growth. Additionally, rising prevalence of chronic diseases globally is increasing the for advances inmedicaltechnologies, thus pushing the growth further. Moreover, factors such as rising health awareness, developinghealthcare infrastructure, growing geriatric population, and the inflatingdisposableincomes are expected to propel the market in the forecast period.

Industry Definition and Major Segments

Stem cells are undifferentiated cells present in bone marrow,umbilical cordadipose tissue and blood. They have the ability to of differentiate and regenerate. The process of storing and preserving these cells for various application such as gene therapy, regenerative medicine and tissue engineering is known as stem cell banking.

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By service type, the market is divided into:

Based on product type, the industry can be segmented into:

The market is bifurcated based on utilization into:

By bank type, the industry can be broadly categorized into:

Based on application, the industry can be segmented into:

On the basis of regional markets, the industry is divided into:

1 North America1.1 United States of America1.2 Canada2 Europe2.1 Germany2.2 United Kingdom2.3 France2.4 Italy2.5 Others3 Asia Pacific3.1 China3.2 Japan3.3 India3.4 ASEAN3.5 Others4 Latin America4.1 Brazil4.2 Argentina4.3 Mexico4.4 Others5 Middle East & Africa5.1 Saudi Arabia5.2 United Arab Emirates5.3 Nigeria5.4 South Africa5.5 Others

Market Trends

Regionally, North America is projected to dominate the global stem cell bank market and expand at a significant rate. This can be attributed to increasing research and development for stem cell application in various medical fields. Further, growing investments of pharmaceutical players and development infrastructure are other factors that are expected to stem cell bank market in the region. Meanwhile, Asia Pacific market is also expected to witness fast growth owing to the rapid development in healthcare facilities and increasing awareness of stem cell banking in countries such as China, India, and Indonesia.

Key Market Players

The major players in the market are Cryo-Cell International, Inc., Smart Cells International Ltd., CSG-BIO Company, Inc., CBR Systems Inc., ViaCord, LLC, LifeCell International Pvt. Ltd., and a few others. The report covers the market shares, capacities, plant turnarounds, expansions, investments and mergers and acquisitions, among other latest developments of these market players.

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Expert Market Research is a leading business intelligence firm, providing custom and syndicated market reports along with consultancy services for our clients. We serve a wide client base ranging from Fortune 1000 companies to small and medium enterprises. Our reports cover over 100 industries across established and emerging markets researched by our skilled analysts who track the latest economic, demographic, trade and market data globally.

At Expert Market Research, we tailor our approach according to our clients needs and preferences, providing them with valuable, actionable and up-to-date insights into the market, thus, helping them realize their optimum growth potential. We offer market intelligence across a range of industry verticals which include Pharmaceuticals, Food and Beverage, Technology, Retail, Chemical and Materials, Energy and Mining, Packaging and Agriculture.

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Global Stem Cell Banking Market To Be Driven At A CAGR Of 13.5% In The Forecast Period Of 2021-2026 ManufactureLink - ManufactureLink

Bone Marrow Stem Cells Comments Off on Global Stem Cell Banking Market To Be Driven At A CAGR Of 13.5% In The Forecast Period Of 2021-2026 ManufactureLink – ManufactureLink | May 29th, 2022

The latest release titled Rheumatoid Arthritis Stem Cell Therapy Market Research Report 2022-2028 (by Product Type, End-User / Application, and Regions / Countries) provides an in-depth assessment of the Rheumatoid Arthritis Stem Cell Therapy including key market trends, upcoming technologies, industry drivers, challenges, regulatory policies, key players company profiles, and strategies. Global Rheumatoid Arthritis Stem Cell Therapy Market study with 100+ market data Tables, Pie Chat, Graphs & Figures is now released. The report presents a complete assessment of the Market covering future trends, current growth factors, attentive opinions, facts, and industry-validated market data forecast until 2028.

A sample report can be viewed by visiting (Use Corporate eMail ID to Get Higher Priority) at: https://www.stratagemmarketinsights.com/sample/42901

Global Rheumatoid Arthritis Stem Cell Therapy Market and Competitive Analysis:

Know your current market situation! Not only an important element for new products but also for current products given the ever-changing market dynamics. The study allows marketers to stay in touch with current consumer trends and segments where they can face a rapid market share drop. Discover who you really compete against in the marketplace, with Market Share Analysis know market position, % Market Share, and Segmented Revenue of Rheumatoid Arthritis Stem Cell Therapy Market.

Moreover, it will also include the opportunities available in micro markets for stakeholders to invest, a detailed analysis of the competitive landscape, and product services of key players. Analysis of Rheumatoid Arthritis Stem Cell Therapy companies, key tactics followed by Leading Key Players:

Mesoblast, Roslin Cells, Regeneus, ReNeuron Group, International Stem Cell Corporation, Takeda

Market Segments by Type:

Allogeneic Mesenchymal Stem Cells, Bone Marrow Transplant, Adipose Tissue Stem Cells

Market Segments by Application:

Hospitals, Ambulatory Surgical Centers, Specialty Clinics

The base on geography, the Rheumatoid Arthritis Stem Cell Therapy market has been segmented as follows:

North America includes the United States, Canada, and MexicoEurope includes Germany, France, the UK, Italy, SpainSouth America includes Colombia, Argentina, Nigeria, and ChileThe Asia Pacific includes Japan, China, Korea, India, Saudi Arabia, and Southeast Asia

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The Study Objectives are:

A comprehensive insight into key players operating in the Rheumatoid Arthritis Stem Cell Therapy market and their corresponding data. It includes product portfolio, annual revenue, expenditure on research and development, geographical presence, key developments in recent years, and growth strategies. Regional analysis, which includes insight into the dominant market and corresponding market share. It also includes various socio-economic factors affecting the evolution of the market in the region. The report offers a comprehensive insight into different individuals from value chains such as raw materials suppliers, distributors, and stockholders.

Key Opportunities:

The report examines the key opportunities available in the Rheumatoid Arthritis Stem Cell Therapy market and outlines the factors that are and will be driving the growth of the industry. It considers the previous growth patterns, the growth drivers, and the current and future trends.

Pricing and Forecast

Pricing/subscription always plays an important role in buying decisions; so we have analyzed pricing to determine how customers or businesses evaluate it not just in relation to other product offerings by competitors but also with immediate substitute products. In addition to future sales Separate Chapters on Cost Analysis, Labor*, production*, and Capacity are Covered.

(Note: * if Applicable)

Key Questions Answered:

1. What is the market size and CAGR of the Rheumatoid Arthritis Stem Cell Therapy market during the forecast period?2. How is the growing demand impacting the growth of Rheumatoid Arthritis Stem Cell Therapy market shares?3. What is the growing demand of the Rheumatoid Arthritis Stem Cell Therapy market during the forecast period?4. Who are the leading vendors in the market and what are their market shares?5. What is the impact of the COVID-19 pandemic on the APAC Rheumatoid Arthritis Stem Cell Therapy market?

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Rheumatoid Arthritis Stem Cell Therapy Market Growth: 2022, Observing High Industry Demand and Business Trends Carbon Valley Farmer and Miner -...

Bone Marrow Stem Cells Comments Off on Rheumatoid Arthritis Stem Cell Therapy Market Growth: 2022, Observing High Industry Demand and Business Trends Carbon Valley Farmer and Miner -… | May 29th, 2022

A Bishop's Stortford family's story of navigating the emotional, physical and financial challenges of living with blood cancer, by Amy Gannon

Cancer has been in the press a lot lately. With cancer care in the NHS still suffering from the Covid pandemic causing disruption to health services, the cancer backlog is still very much a concern.

Now, more than ever, it is so important to promote cancer awareness and encourage people to get help and go to their GP if they feel something is not right.

Headlines have been full of Deborah James known online as BowelBabe being made a dame for her tireless efforts to promote awareness of cancer. Whilst receiving end-of-life care for her terminal bowel cancer she has raised over 6 million for cancer research. She is truly an inspiration. Her sheer lust for life and desire to continue living is just so pure and inspiring.

My fianc Joels blood cancer diagnosis has changed the whole way we view the world. This year showed me life is not just something you wake up to, it is not just a given.

Life is something you have to fight for, and if youre not fighting for it, if youre just inhaling and exhaling and walking through this world without a worry, then you truly have everything.

After a tough appointment with Joels consultant, who told us that for a cure Joel would most likely need a bone marrow transplant, we had a big think about the way we wanted to spend now.

The consultant said: "You need to start living for now, not in fear of the battle that is to come."

Those words stayed with me as we walked down the corridors of Addenbrooke's Hospital in Cambridge to the car. Those corridors hold so many memories. The words said and treatments given in the rooms off those corridors hold so much power over peoples lives, emotions and existence.

Our appointment really highlighted to me the importance of bone marrow and stem cell donors. With only 30% of patients able to find a compatible donor within their family, it is so important to have people of all ages and races signed up to the donor register.

DKMS is a charity dedicated to fighting blood cancer and blood disorders, giving people a second chance at life through its donor database.

To register to donate stem cells, it couldnt be easier: go to the DKMS website and register online. Youll be sent a swab kit. Simply swab your cheeks and return to DKMS. Once your swab has been analysed you will be added to the register and available to save the life of someone anywhere in the globe!

With a transplant potentially on the horizon and the consultants words ringing in our ears, we decided to get away for the week. We headed to Center Parcs to be among the trees and nature. We turned off our phones and focused on us.

Watching Joel walk alongside other people, he looks a picture of health. He blends into the flow of the crowd. Nothing notable that screams I have cancer. Sometimes, for a moment, I forget that he has cancer all together.

While the majority of the country has ditched masks and returned mainly to normal, we still have to be very careful. We lateral flow test regularly, avoid crowded places and still wear masks. We have to trust in people making the right decisions; immuno-compromised people were somewhat neglected when the Government stopped compulsory isolating and access to free tests.

The reassurance and protection that frequent testing and isolating if Covid positive offered societys medically vulnerable have vanished, and trying to socialise in safe ways has become even more challenging.

This last fortnight has taught us to stop just existing and actually start living life with Joels leukaemia.

To anyone battling this cruel illness, you are more than your cancer. Cancer is part of your life but it doesnt define you.

Living alongside cancer is tough, but that doesnt mean it has to be all your life is about. You can still be yourself let your old self shine through the illness.

Sure, life has to change in certain ways; benefit versus risk has to be weighed up a lot. There are many challenges and its not easy, but I promise you can still find ways to be happy.

You can strive to not just simply exist but to actually live with cancer.

READ ALSO Home from hospital for Christmas... the daddy that 4-year-old Isla hasn't been able to cuddle for over four months

READ ALSO Life with Leukaemia: 'After a misdiagnosis, we were fighting leukaemia with hot water bottles and paracetamol'

READ ALSO Walk of Light in aid of Blood Cancer UK: Isla and I walking in step with our friends to live in a world free of blood cancer

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Life with Leukaemia: The consultant's words that made us think about how we spend our 'now' - Bishop's Stortford Independent

Bone Marrow Stem Cells Comments Off on Life with Leukaemia: The consultant’s words that made us think about how we spend our ‘now’ – Bishop’s Stortford Independent | May 29th, 2022

Osteoarthritis (OA) is the most common type of arthritis[1], and it is characterized by a progressive loss of articular cartilage, subchondral bone edema, sclerosis, synovitis, and marginal osteophyte formation. Pain, stiffness, and a restriction in joint movement are the most common symptoms whose severity varies. However, the condition gradually worsens over time and often results in significant functional impairment and reduced quality of life[2,3]. It was anticipated to become the fourth leading cause of disability by 2020[1,4,5], posing a significant socioeconomic burden impacting developed countries' gross domestic product[1,6]. Knee osteoarthritis (KOA) accounts for 85 percent of the global burden of OA and affects 19% of adults over 45-year-old and 37% of people over 60. KOA produces significant pain and physical impairment, lowering the quality of life and ranking as the eleventh leading cause of global disability. The average annual total expense per KOA patient is over US$15 000, resulting in total healthcare expenditure of nearly US$34 billion. Given population aging and the rise in obesity, KOA healthcare expenses are expected to quadruple by 2040[7]. It is necessary to develop sufficient medicines capable of slowing the progression of the disease and, as a result, preventing the loss of articular function and joint replacement. To provide more effective therapies, current conservative choices such as exercise and physiotherapy and weight loss with analgesics and naturally occurring substances should be integrated[1,8]. Developing effective conservative methods would be especially important for treating young people with early OA because their more active and physically demanding lifestyle negatively correlates with prosthetic implant survival[1,9].

The main treatment in the clinic is non-steroidal anti-inflammatory drugs (NSAIDs), which are recommended for all patients except those having surgical treatment in the American Academy of Orthopaedic Surgeons (AAOS) clinical practice recommendations for KOA treatment[10-12]. However, long-term usage of these treatments will cause major adverse reactions in patients, such as gastrointestinal ulcers, digestive system hemorrhage, and cardiovascular and cerebrovascular side effects, regardless of the toxicity of the drugs themselves[10,13]. Intra-articular injections of HA, platelet-rich plasma (PRP), or corticosteroids (CC) are also clinical possibilities, but their efficacy and the prevalence of side effects are still debated[10,14,15].

MSCs, be a possible treatment option for KOA[16-20]. MSCs, also called MPCs, secrete various cytokines that modulate an anti-inflammatory milieu in the OA joint, giving them immunomodulatory characteristics[18,21]. They may also have a unique ability to induce the growth of new cartilage-like cells in vitro[17,18,22], as improvements in cartilage morphology have been found in some situations[23-26]. These characteristics make them a suitable candidate for use in knee cartilage repair[27-32]. For OA treatment, orthobiologics injections containing MSCs as effector cells have recently been used. Because of their accessibility, bone marrow (BM) and adipose tissue (AD) have traditionally been the most used autologous tissue sources for orthopedic usage. In several studies, the use of autologous orthobiologics treatments in the treatment of OA is safe, with an extensive multicenter prospective analysis revealing no higher risk of neoplasia[33,34].

MSCs treatment looks to be safe based on published clinical study results. There were no significant side effects other than transitory fever in a comprehensive systematic review and meta-analysis of trials involving intravascular delivery of autologous or allogeneic expanded MSCs treatments (totaling over 1000 participants)[35,36]. A systematic evaluation of clinical trials involving intra-articular autologous expanded MSCs therapy that included 844 procedures. They had a mean follow-up of 21 months and found no link between infection, cancer, or death[35,37].

As a result, we undertook this study to examine all current high-quality information on the therapeutic efficacy and safety of MSCs in the treatment of KOA qualitatively and quantitatively. This is crucial, and the study's findings will give evidence and recommendations for the promotion and deployment of MSCs therapy in clinical practice.

We developed and implemented the study according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) system[38], the review's preferred reporting items.

Database

On December 30, 2021, we began our research using online libraries as a database. For our data gathering, we used PubMed, the Cochrane Library, and PMC.

Search Strategy

We included studies related to KOA, MSCs, and intra-articular injection. Our keywords and medical subject heading (MeSH) search strategies included knee, osteoarthritis, mesenchymal stem cells, intra-articular, and injection. The main MeSH terms used were: ("injections, intra articular"[MeSH Terms] OR ("injections"[All Fields] AND "intra articular"[All Fields]) OR "intra-articular injections"[All Fields] OR ("intra"[All Fields] AND "articular"[All Fields] AND "injection"[All Fields]) OR "intra articular injection"[All Fields]) AND ("mesenchymal stem cells"[MeSH Terms] OR ("mesenchymal"[All Fields] AND "stem"[All Fields] AND "cells"[All Fields]) OR "mesenchymal stem cells"[All Fields]) AND ("osteoarthritis, knee"[MeSH Terms] OR ("osteoarthritis"[All Fields] AND "knee"[All Fields]) OR "knee osteoarthritis"[All Fields] OR ("knee"[All Fields] AND "osteoarthritis"[All Fields])) and Knee Osteoarthritis, Mesenchymal Stem Cells, Intra-articular Injections. MeSH terms carried out a further supplementary search with free words. In addition, to prevent eliminating papers that satisfied the inclusion criteria, we searched retrieved studies that were cited.

Inclusion Criteria

We included RCTs and clinical trial studies conducted between 2017-and 2021, with complete free texts in the English language from all countries. Also, men and women aged 18 years or older with osteoarthritis in their knees and the severity of their osteoarthritis are shown in KL grade.

Exclusion Criteria

We excluded studies before the last five years, not in English, that included animals, HA, PRP, arthroscopy, ultrasound waves, and combination treatment in the intervention, other than knee joints like shoulder and hip.

Quality Assessment Tools

Two authors, S.S and S.V, independently assessed the study's overall quality and risk of bias by using the Cochrane Collaboration risk-of-bias tool for the RCTs and Newcastle Ottawa Scale (NOS) for the clinical trials. The Cochrane Collaboration risk-of-bias tool included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Each included RCT was rated as having a low, unclear, or high risk of bias based on these factors. The following are the contents for the NOS, including selection, comparability, and outcome. According to these items, each included clinical trial was scored as good, fair, and poor quality.

Data Extraction

Two writers, S.S and S.V, worked independently to extract data using a standardized manner. Disagreements that arose during the procedure were resolved through debate between the two writers or contact with a third author, just as they were with the inclusion of literature into the study. The following were the contents of the data extraction form: the first author's name, the year of publication, the sample size, basic patient information (age, male-to-female ratio, body mass index (BMI)), osteoarthritis grading KL grade, donor source (autogenous/allogeneic), cell processing, culture, and harvesting, number of cells, immunophenotype, intervention, and control situation, follow-up, and outcome clinical effectiveness and safety were among the outcomes.

Literature Search

Using the literature search, we discovered 78 relevant papers. After eliminating duplicates and screening titles and abstracts, 50 articles were excluded. The remaining 18 articles were subjected to a full-text review, with eight being excluded, as shown in figure1.

Characteristics of the Included Studies

A total of six RCTs (577 participants)[2,7,17,18,32,35], including one study which had a pilot study, commenced in November and completed in June 2021, where recruitment commenced in January and August 2021 and will be finished by December 2024[7]. Four clinical trial studies, including three prospective[16,23,32], and one retrospective[33]clinical trial, were included in this systematic review. Publication intervals for all 10 were from 2017 to 2021[7]. All studies used autologous MSCs except two studies[2,7], which used allogeneic MSCs. Five studies[2,17,18,35,39], used AD-MSCs two studies[23,32], used BM-MSCs, one study[16], used BMA, one study[33], used both concentrations BMAC and MFATand one study[7], used multipotent MSCs. A placebo was utilized as a control group[2,39]. For one study, NS was used as the control group[7]; for one trial, HA was used as the control group[17], In one study's control group, cautious management was adopted[35], and five of the investigations[16,18,23,32,33], were uncontrolled. Furthermore, four trials[2,16,17,35]were monitored for a year, three trials[7,23,32]were monitored for 24 months, and two trials[33,39]were followed for six months after they were completed, and one study[18], had a 48-weeks follow-up period. Table1illustrates the features of the 10 articles that were featured.

Risk of Bias Assessment

Figure2shows the results of the risk of bias evaluation for six studies[2,7,17,18,35,39], while table2shows the results of the NOS for four studies[16,23,32,33]. Lee et al.[39], although relevant images were drawn, we could not retrieve the original data and conduct the combined statistics; hence this study was classified as having a high risk of reporting bias. Freitag et al. and Kuah et al. incomplete data on overall WOMAC scores and subscales (pain, stiffness, and function) were also given, and one or more of these characteristics may have been missing. As a result, attrition bias was found to be considered a risk in these two investigations[2,35]. Freitag et al. performed BM or subcutaneous tissue extraction only in the intervention group. Even though moral restraint precluded the same measures from being used in the control group, this study was classified as having a high risk of detection and performance bias[35].

Outcomes

Knee Injury and Osteoarthritis Outcome Score (KOOS): A total of seven studies[7,16,23,32,33,35,39]reported KOOS[40]at baseline and final follow-up in the intervention and the control groups, including 650 patients. Three studies[7,23,32] were followed up for 24 months, two studies[16,35]were followed up for 12 months, and two studies[33,39]were followed up for six months. Normalized KOOS was used to measure positive changes in all five primary areas, and all were significantly better at six, 12, and 24-months post first injection[32]. Significant improvements in Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scores were observed over time (F (4,12) =12.29, p<0.001) in a cohort. Following the procedure, clinical significance was accomplished at three, six, and 12-months following the procedure[16]. As evaluated by normalized KOOS, table3demonstrates the favorable changes in all five essential categories. All were much improved at six, 12, and 24 months after the first treatment[32]. Using all sample time points, the Sport Score and quality of life (QOL) score were nominally linked with an unadjusted p-value of 0.031 and 0.046, respectively[23].

Magnetic Resonance Imaging (MRI) Evaluation

A total of eight studies reported MRI evaluation at baseline and follow-up in the groups, including 659 patients[2,7,17,18,23,32,33,39]. Three studies[7,23,32]were followed for a total of 24 months, for 12 months, two studies[2,17]were followed up on, and two studies[33,39]were followed up for six months after they were completed, and one study[18], had a 48-weeks follow-up period. The transformation of the central medial femorotibial compartment (cMFTC) cartilage thickness[41]for a 24-month was 0.32 mm (SD=0.40) for those who have narrowed medial tibiofemoral joint and maintained knee pain at baseline in comparison to the control neither of which radiographic nor pain development (0.12mm, SD=0.28)[7,42]. 67 percent of patients had progressed cartilage degeneration within the control group, with another 56 percent having extended osteophyte formation. Only 30% of individuals saw additional cartilage loss in the one-injection group, whereas 50% experienced osteophyte development advancement at 12 months. In the two-injection group, 89 percent of participants had cartilage improvement or no progression in cartilage loss, indicating that OA had stabilized, as seen by 89 percent of subjects having no progression in osteophyte formation[35]. The size of the cartilage defect in the MSCs group did not change substantially on MRI at six months (p =.5803), but the size of the cartilage defect in the control group grew significantly (p =.0049). Furthermore, the change in cartilage defect following the injection was significantly different between the two groups (p =.0051)[39]. Using the WORMS technique, the low-dose group had a mean change from baseline of -0.36 and -0.86 in both the left and right knees at week 48. Furthermore, the mean changes in total cartilage volume, knee femur end cartilage volume and knee patellar cartilage volume in the low-dose group were 54.58, 38.63, and 39.69 mm, respectively. The knee tibial end cartilage volume and knee cartilage volume in the medium-dose group improved by 243.32 and 34.44 mm, respectively. Increases of -0.42 and 122.92 mm in the left knee WORMS and knee femur end cartilage volume were reported in the high-dose group[18].

Two bilateral intra-articular knee injections, three weeks apart (18-20 days), were used in this preclinical study with AlloJoin. Because the high prevalence of bilateral KOA in the treatment population was investigated[18,43,44]. MRI showed no significant change in cartilage thickness after six months. As indicated in Table4, there was a considerable improvement in knee cartilage thickness in the femoral and tibia plates after 12 months[32]. Time 2 (T2) scores in the patella region increased by a negligible amount (p =.055 for a two-sided test, nonadjusted). T2 changes (from baseline to 12 months) did not differ across the one, 10, or 50 million BM-MSCs cohorts[23]. The 50 million BM-MSCs doses (effect estimate [B] = 1.828, p =.002) maintained synovitis at lower levels than the one million BM-MSCs dose, according to statistical analysis of the effects of dose adjusted for both time and baseline levels of synovitis[23]. We found a decrease in pro-inflammatory monocytes/macrophages in synovial fluid three months after MSCs infusion, suggesting a potential mechanism of action. We do not see statistical significance relative to baseline levels (p =.062) because of the small number of patients who presented synovial fluid at baseline and three months after MSC infusion (n = 5). However, this downregulation suggests a potential mechanism of action of MSCs in the arthritic joint[23].

Visual Analogue Scale (VAS)

A total of five studies[2,17,18,33,39]reported VAS evaluation at baseline and follow-up in the groups, including 194 patients. Two studies[2,17]were followed up for 12 months, two studies[33,39]were followed up for six months, and one study[18]was followed up for 48 weeks. VAS32[7], (P < .00001)[10], (p 0.005) in Progenza (PRG) combined group[2]. In the MSCs group exclusively, the VAS for knee discomfort dropped dramatically from 6.8 0.6 to 3.4 1.5 (p.001)[39]. Our VAS data confirmed clinical improvement with these cell injections, as seen by the study's reported VAS minimal clinical improvement differences (MCID) score of 30.0 mm[18,45,46].

Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC)

A total of six studies[2,17,18,23,35,39]reported WOMAC[47], evaluation at baseline, and follow-up in the groups, including 160 patients. Three studies[2,17,35]were tracked for 12 a year, one trial[23]was monitored for 24 months, one study[18]had a 48-weeks follow-up period, and for six months, one trial[39]was followed. (All P values were less than .05)[10]. Also, compared to the HA group, significantly more individuals had a 50% improvement in WOMAC, and after 12 months, the Re-Join group had a 70% improvement rate, indicating that more patients were improving[17].

At six months after injection, a single injection of AD-MSCs resulted in a 55 percent reduction in the WOMAC total score, a 59 percent reduction in the WOMAC pain score, a 54 percent reduction in the WOMAC stiffness score, and a 54 percent reduction in the WOMAC physical function score[39]. According to a study in previous research[24,48-50], clinical outcomes improved six months following MSCs injection. The findings of this investigation support this. Furthermore, similar to earlier research[49,50], even six months following injection, the clinical outcomes were still good. This finding implies that with a single intra-articular MSCs injection, symptom alleviation can be sustained for up to six months[39]. Improvements in short form 36 (SF-36), -23.71 in WOMAC total, -17.14 in WOMAC-function, -2.29 in WOMAC stiffness, and -4.29 in WOMAC-pain were seen in the low-dose cohort. Improvements in left knee VAS were -2.25, right knee VAS was -2.13, WOMAC-total was -16.50, WOMAC-function was -11.88, WOMAC-stiffness was -1.71, and WOMAC-pain was -3.25 in the medium-dose cohort. The high-dose cohort observed statistically significant improvements in the left knee VAS of -1.36 and the right knee VAS of -2.07[18]. The MCID averages for the WOMAC with KOA have been published[51]. The WOMAC functional score ranges between 9.1 to 19.9 mm, indicating that the WOMAC scores in this trial indicated considerable clinical improvement for the overall WOMAC functional (17.1) for both the left and right knees after 48 weeks for two of the doses[18,52-55].

Adverse Events (AEs)

A total of four studies[7,16,17,32]reported AEs evaluation at baseline and follow-up in the groups, including 550 patients. Two studies[7,32]were followed up for 24 months, and the others[16,17]were followed up for 12 months. Patient satisfaction was high (range: 8.12.1-8.81.9). All the patients said they would recommend the treatment to a friend, and 85 percent said they would do it again[16]. In the MSCs group, 10 (83%) patients experienced AEs, compared to seven (58%) individuals in the control group. No significant AEs or grade 4 or 5 AEs on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale. All the grade 3 AEs on the NCI-CTCAE scale were arthralgia, which completely disappeared within three days[39,56]. In the low-, middle-and high-dose groups, the incidence of AEs was 71.42 percent (5/7), 87.50 percent (7/8), and 100 percent (7/7), correspondingly[18].

We evaluated the clinical efficacy and safety of intra-articular injection of MSCs in this study by thoroughly analyzing six RCTs and four clinical trials. The study's first strength is its comprehensiveness, a compilation of all current high-quality studies. Second, we assessed the included studies' cell adherence, cell immunophenotype, and cell differentiation ability using the MSC criteria established by the Mesenchymal Stem Cell Committee of the International Society for Cell Therapy (ISCT), and discovered that half of them meet the minimum requirements[16,18,23,35,39], as shown in table1. Third, it contains tight inclusion and exclusion rules. Concurrent therapy studies, such as HA and PRP were omitted. The addition of newly incorporated research of AT and BM sources, we believe, is what has led to the divergent results. This is one of the reasons we are so adamant about completing this research. Compared to the control group, the MSCs group showed a considerable increase in cartilage volume.

The selection of the appropriate donor source and the optimal dose has become an essential issue due to the extensive research into MSCstherapy. BM, AT, placenta, and umbilical cord are among the most popular donor sources for MSCs in clinical research. Initially, people preferred to cultivate and expand BM-MSCs. Later research discovered that AT was more accessible than BM, had a simpler isolation technique, a larger yield, and the same chondrogenic capacity[10,57,58].

A reduction in pain is connected to the ability of cells to release bioactive chemicals. These elements are hypothesized to change the inflammatory milieu in the joint from pro-inflammatory to anti-inflammatory. PRG includes a high concentration of these bioactive substances in the cell culture supernatant, unlike other cell therapies. PRG may decrease the progression of OA based on the favorable cartilage outcomes from preclinical and clinical investigations. Many studies have found that beneficial effects are primarily apparent in the lateral tibial region. Although OA affects the entire joint, it has been hypothesized that the medial tibiofemoral region is more severely damaged than the lateral tibiofemoral region. As a result, because the medial tibiofemoral region is later, there may be fewer opportunities to demonstrate progress[2].

MPCs tagged with fluorescent dye lasted locally in the joint for up to 10 weeks in preclinical rat studies before becoming undetectable[18,59]. Furthermore, the serious adverse events (SAEs) contradict all preclinical animal investigations that revealed no evidence of systemic exposure[18,59-61]. In addition, earlier research has shown that Re-Join is beneficial in rabbit and sheep models of OA[17,60,61]. The repair of osteoarthritis in rabbits and goats appears to be mediated by paracrine effects involving the stimulation of endogenous repair systems[26,32]. In a systematic evaluation of MSCs therapies, Lalu et al. found no significant side effects[23,62,63]. Following the aspiration of BM, there were no systemic side effects observed, and there were no issues that were noted[23]. Therefore, no individuals dropped out of the study[2].

Our findings show that there are statistically significant improvements in pain and function[2,7,10,16-18,33,35]. The average percentage of patients who have passed the Patient-Acceptable Symptom State (PASS)[64]the threshold was 35% in the placebo cohort(ranging from 33.1 to 35.5) and 48% in the intervention cohorts (varying between 42.2% to 56.1%)[7,65,66]. There were also decreases in present, typical, best, and worst numerical rating scale (NRS) pain[67], scores statistically significant over time (F(4,12)=14.5, p<0.001; F(4,12)=17.5, p<0.001; F(4,12)=2.9, p=0.003; and F(4,12)=35.5, p<0.001, respectively)[16]. Also, NRS pain in both the single and two injection protocol treatment groups, when compared to baseline, within-group improvement was statistically significant (0.05) at all time intervals[35]. Therefore, we found that all statistical tests for pain and functional outcome measures (n = 21) had a mean power of 0.877 15 SD[35]. The NPRS improved by 69 percent from baseline to the last follow-up at 12 months in both therapy groups. In comparison, arthroscopic debridement resulted in a 14 percent improvement in pain scores after 12 months, while a prescribed exercise regimen resulted in a 12 percent improvement in pain scores[35,68,69]. The range of motion in the MSCs group improved considerably from 127.9 10.3 to 134.6 12.5 at six months after injection (p =.0299)[39]. When these established MCID values were applied at 48 weeks, there was a reduction in pain and an improvement in knee function; however, due to the small number of participants included in this pilot investigation, these findings should be regarded with caution[18].

In addition, they discovered a link between the number of cells injected and pain relief[33]. Furthermore, two RCTs were recently reported, revealing significant improvements in pain and function in KOA patients after injection of autologous AD-MSCs versus controls[33]. MSCs generated from autologous BM showed a significant increase in clinical ratings[33,39]. Because the researchers differ in study design, cell type, supplementary therapy, and rehabilitation methods, it is difficult to determine the true differences in intra-articular injections of BM-MSCs and AD-MSCs[39].

Data reveal that one or more outcomes, such as KOOS pain, have improved statistically significantly[23,32,35], symptoms, SF-36[18], VAS[2,10,16,18,33,39], and QOL scores[17,23,33], as well as WOMAC stiffness[2,10,16-18,23,33,35,39]. NPRS improved[16,35], from baseline to final follow-up at 12 months, by a percentage of 69 percent previous clinical trials have shown that intra-articular MSCs treatment can slow the course of OA[35]. All symptoms decreased dramatically, resulting in a considerable improvement in the quality of life of these grade 2 to 4 KOA patients. There is also evidence of safety. However, more research is required. Another concern is that most research focuses on short-term safety rather than long-term results[32]. Starting three months after the procedure, KOOS-JR scores improved dramatically, with clinically meaningful improvements lasting 12 months[16]. Within 48 weeks of follow-up, MCID scores for SF-36 are approximately 10%, which this study's data has surpassed[18,53,70,71]. Both groups improved significantly in Emory Quality of Life (EQOL), VAS, and all KOOS indicators pre-and post-procedure (p < .001)[33]. During follow-up, the two treatment groups' EQOL ratings altered in similar ways (similar temporal patterns across time) (p =0.98, test for interaction between time on study and treatment group)[33].

We report putative chondroprotective benefits and decreased synovial inflammation, with the 50 million cell dosage potentially being more beneficial. However, when compared to the 50 million and/or 10 million BM-MSC dosages, serum carboxy-terminus of the three-quarter peptide from cleavage of C I and C II (C1, C2), urine type II collagen cleavage neoepitope (C2C), and C-telopeptide of type II collagen (CTX-II) all increased significantly, suggesting a chondroprotective MSCs dose effect, as previously described[23]. Furthermore, exploratory MRI analyses of average cartilage volumes and average WORMS from baseline at week 48 revealed no change in the medium-dose (2*107 cells) and high-dose (5*107 cells) groups but an improvement in the low-dose AlloJoin (1*107 cells) group[18]. Over radiography x-rays, MRI assessments offered a more accurate picture of articular cartilage deterioration and change in location of the menisci[18,72]. Because MOAKS[73]is a semi-quantitative metric, the MRI analysis is limited[18]. Furthermore, MOAKs analysis demonstrating effective stabilization despite continuous bone marrow lesions (BMLs)contrasts with previous research that has found a link between BMLs and OA progression[35].

Because Orozco et al. showed a consistent improvement in cartilage quality during a two-year follow-up period from the baseline, we expect cartilage improvement in our series over a longer follow-up time[39,48]. Our research also saw increased cartilage volume and quality[2,17,18,23,32,39]. Furthermore, an MRI examination at 48 weeks revealed no signs of ectopic bone development[18]. Intra-articular injections of Re-Join were found to enhance cartilage volume, with a significant rise 12 months after injection, suggesting that this could be a viable therapeutic intervention and cartilage regeneration for OA patients[17].

We believe that the subsequent trials should be greater[23]. The following trials should, in our opinion, be larger[18]and also look at the MSCs dose and the MSCs source. The safety of allogeneic MSCs for KOA must be established[23,32,39]. The usage of allogenic MSCs can be standardized, the dose can be more precisely regulated, and cell variability may be minimized. We should also examine the efficacy of BM and AD-derived orthobiologics treatments to develop a reliable judgment on which is the better choice for treating KOA[33]. MSCs, we feel, has the potential to be a definitive treatment for KOA[32]. It is also critical to distinguish the findings of this study from those of previous studies that used more various cell-based products, such as stromal vascular fraction[35].

This research has several limitations. The results should be treated with care first and foremost. We did our utmost to avoid simultaneous surgical treatment affecting efficacy. Second, all the studies we looked at used intra-articular injections. MSCs implantation by open or arthroscopic surgery has been proven to be more conducive to cartilage repair in several studies. While MSCs transplantation on a scaffold may help rebuild the anterior cruciate ligament and meniscus[10]. Third, four of our studies[16,23,32,33], were not RCTs. Fourth, we included three studies[23,33,39]that included KL grade 4 KOA patients. We do not know if the disease can be slowed or even reversed at this point in the disease's progression, especially using autologous-derived MSCs. Furthermore, as the human body ages, MSCs' ability to self-renew and differentiate decreases; particularly, the potential of MSCs in individuals with OA is lower than that of healthy persons[10,17,23,33,35].

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You should read the following discussion and analysis of our financial conditionand results of operations together with the condensed consolidated financialstatements and related notes included in Part I, Item 1 of this Quarterly Reporton Form 10-Q (this "Quarterly Report") and with the audited financial statementsand the related notes included in our Annual Report on Form 10-K for the fiscalyear ended December 31, 2021 filed with the Securities and Exchange Commissionon March 18, 2022. Certain of the information contained in this discussion andanalysis or set forth elsewhere in this Quarterly Report, including informationwith respect to plans and strategy for our business, includesforward-looking statements that involve risks and uncertainties. As a result ofmany factors, including those factors set forth in the section entitled "RiskFactors", in Part II, Item 1A of this Quarterly Report, our actual results coulddiffer materially from the results described in or implied by theforward-looking statements contained in the following discussion and analysis.You should carefully read the section entitled "Risk Factors" to gain anunderstanding of the important factors that could cause actual results to differmaterially from our forward-looking statements. Please also see the section ofthis Quarterly Report entitled "Cautionary Note RegardingForward-Looking Statements." The events and circumstances reflected in ourforward-looking statements may not be achieved or may not occur, and actualresults could differ materially from those described in or implied by theforward-looking statements contained in the following discussion and analysis.As a result of these risks, you should not place undue reliance on theseforward-looking statements. We assume no obligation to revise or update anyforward-looking statements for any reason, except as required by law.OverviewWe are a clinical-stage biotechnology company dedicated to enabling curesthrough hematopoietic stem cell therapy. We are focused on the development andcommercialization of safer and more effective conditioning agents and mRNA-basedstem cell engineering to allow for expanded use of stem cell transplantation andex vivo gene therapy, a technique in which genetic manipulation of cells isperformed outside of the body prior to transplantation. We are also developingnovel therapeutics directed at diseased hematopoietic stem cells.Our drug development pipeline includes multiple product candidates designed toimprove hematopoietic stem cell therapy. Our lead product candidate, JSP191, isin clinical development as a novel conditioning antibody that clearshematopoietic stem cells from bone marrow in patients prior to undergoingallogeneic stem cell therapy or stem cell gene therapy. We plan to initiate aregistrational clinical study in acute myeloid leukemia ("AML") patientsundergoing stem cell transplantation by the end of the first quarter of 2023.Based on the single agent depletion observed in our Phase 1 study ofmyelodysplastic syndrome ("MDS") patients undergoing stem cell transplant, weare also initiating a pilot study of JSP191 as a therapeutic in lower-risk MDS,which we expect to commence in the second half of this year. Beyond JSP191, weare developing stem cell grafts transiently reprogrammed using mRNA that have acompetitive advantage over endogenous hematopoietic stem cells ("HSCs"),enabling higher levels of engraftment designed to remove the need for highlytoxic conditioning of the patient and lower the risk of other seriouscomplications that limit current stem cell transplants. We plan to continue toexpand our pipeline to include other novel stem cell therapies based on immunemodulation, graft engineering and cell or gene therapies. Our goal is to expandthe use of curative stem cell transplant and gene therapies for all patients,including children and the elderly.Stem cell transplantation is among the most widely practiced forms of cellulartherapy and has the potential to cure a wide variety of diseases, includingcancers, genetic disorders, and autoimmune diseases. Yet currently, patientsmust receive highly toxic and potentially life-threatening conditioning agentsto prepare their bone marrow for transplantation with either donor stem cells ortheir own gene-edited stem cells. Younger, fitter patients capable of survivingthese toxic side effects are typically given myeloablative, or high-intensity,conditioning whereas older or less fit patients are typically given reducedintensity, but still toxic, conditioning which leads to less effectivetransplants. These toxicities include a range of acute and chronic effects tothe gastrointestinal tract, kidneys, liver, lung, endocrine, and neurologictissues. Depending upon the conditioning regimen, fitness of the patient, andcompatibility between the donor and recipient, the risk of transplant-relatedmortality ranges from 10% to more than 50% in older patients. Less toxic ways tocondition patients have been developed to enable transplant for older patientsor those with major comorbidities, but these regimens risk less potent diseaseelimination and higher rates of disease relapse. Even though stem cell therapycan be one of the most powerful forms of disease cure, these limitations ofnon-targeted conditioning regimens have seen little innovation over the pastdecade. 20Our lead product candidate, JSP191, is a monoclonal antibody designed to blockthe specific signal on stem cells required for survival. It is currently indevelopment as a highly targeted conditioning agent prior to stem cell therapyas well as a therapeutics in lower-risk MDS patients, which we expect tocommence in the second half of 2022. We are also sponsoring two clinical studiesof JSP191 as a conditioning agent prior to stem cell transplant. The firstclinical study is an open label Phase 1/2 trial in two cohorts of severecombined immunodeficiency ("SCID") patients: patients with a history of a priorallogeneic transplant for SCID but with poor graft outcomes and newly diagnosedSCID patients. The primary endpoint in this study is to evaluate the safety andtolerability of JSP191. The secondary goal of this study is to evaluate theefficacy of JSP191 as a conditioning agent in conjunction with a stem celltransplant. Based on preliminary results from our ongoing Phase 1/2 clinicaltrial, we believe JSP191 has demonstrated the ability as a single agent toenable engraftment of donor HSCs as determined by donor chimerism, or thepercentage of bone marrow cells in the patient that are of donor origin aftertransplant. Engraftment was observed in seven out of ten T-B-NK+ SCID patientswith prior allogeneic transplant, as evidenced by CD15+ donor chimerism of morethan 5% averaged from 12-24 weeks post-transplant. Increased nave donor T cellproduction was observed in the majority of T-B-NK+ subjects, as well as clinicalimprovement. No JSP191 treatment-related serious adverse events ("SAEs") havebeen reported to date and pharmacokinetics have been consistent with earlierstudies in healthy volunteers. We expect to complete enrollment in this Phase1/2 clinical trial by mid-2023.

The FDA has granted rare pediatric disease designation to JSP191 as aconditioning treatment for patients with SCID. In addition, the FDA grantedorphan drug designation to JSP191 for conditioning treatment prior tohematopoietic stem cell transplantation.

We expect our expenses will increase substantially in connection with ourongoing and planned activities, as we:

? advance product candidates through preclinical studies and clinical trials;

? procure the manufacture of supplies for our preclinical studies and clinical

? attract, hire and retain additional personnel;

? operate as a public company;

? implement operational, financial and management systems;

? pursue regulatory approval for any product candidates that successfully

? establish a sales, marketing, and distribution infrastructure to commercialize

any product candidate for which we may obtain marketing approval and related

commercial manufacturing build-out; and

? obtain, maintain, expand, and protect our portfolio of intellectual property

Business Impact of the COVID-19 Pandemic

Stanford License Agreement

Other collaboration and clinical trial agreements

Collaboration with Stanford University

Components of Results of Operations

External research and development costs include:

? costs incurred under agreements with third-party CROs, CMOs and other third

parties that conduct preclinical and clinical activities on our behalf and

manufacture our product candidates;

? costs associated with acquiring technology and intellectual property licenses

that have no alternative future uses;

? consulting fees associated with our research and development activities; and

? other costs associated with our research and development programs, including

Internal research and development costs include:

? employee-related costs, including salaries, benefits and

stock-based compensation expense for our research and development personnel;

? other expenses and allocated overheads incurred in connection with our research

Our future research and development costs may vary significantly based onfactors, such as:

? the scope, rate of progress, expense and results of our discovery and

preclinical development activities;

? the costs and timing of our chemistry, manufacturing and controls activities,

including fulfilling cGMP-related standards and compliance, and identifying and

? per patient clinical trial costs;

? the number of trials required for approval;

? the number of sites included in our clinical trials;

? the countries in which the trials are conducted;

? delays in adding a sufficient number of trial sites and recruiting suitable

patients to participate in our clinical trials;

? the number of patients that participate in the trials;

? the number of doses that patients receive;

? patient drop-out or discontinuation rates;

? the duration of patient participation in the trials and follow up;

? the cost and timing of manufacturing our product candidates;

? the phase of development of our product candidates;

? the efficacy and safety profile of our product candidates;

? the timing, receipt, and terms of any approvals from applicable regulatory

authorities, including the FDA and non-U.S. regulators;

? maintaining a continued acceptable safety profile of our product candidates

following approval, if any, of our product candidates;

? changes in the standard of care on which a clinical development plan was based,

which may require new or additional trials;

? the extent to which we establish additional strategic collaborations or other

? the impact of any business interruptions to our operations or to those of the

Other Income (Expense), Net

Three Months Ended March 31, 2022 and 2021

The following table summarizes our results of operations for the three monthsended March 31, 2022 and 2021 (in thousands):

Research and Development Expenses

The following table summarizes our research and development expenses for thethree months ended March 31, 2022 and 2021 (in thousands):

Our external costs by program for the three months ended March 31, 2022 and 2021were as follows (in thousands):

General and Administrative Expenses

Liquidity and Capital Resources

Future Funding Requirements - Going Concern

Contractual Obligations and Commitments

We have contractual obligations and commitments as described in Note 9,Commitments and Contingencies, within our condensed consolidated financialstatements included in Part I, Item 1 of this Quarterly Report.

Our future financing requirements will depend on many factors, including:

? the timing, scope, progress, results and costs of research and development,

preclinical and non-clinical studies and clinical trials for our current and

? the number, scope and duration of clinical trials required for regulatory

approval of our current and future product candidates;

? the outcome, timing and costs of seeking and obtaining regulatory approvals

from the FDA and comparable foreign regulatory authorities for our product

candidates, including any requirement to conduct additional studies or generate

additional data beyond that which we currently expect would be required to

support a marketing application;

? the costs of manufacturing clinical and commercial supplies of our current and

future product candidates;

? the costs and timing of future commercialization activities, including product

manufacturing, marketing, sales and distribution, for any of our product

candidates for which we receive marketing approval;

? any product liability or other lawsuits related to our product candidates;

? the revenue, if any, received from commercial sales of any product candidates

for which we may receive marketing approval;

? our ability to establish a commercially viable pricing structure and obtain

approval for coverage and adequate reimbursement from third-party and

? the costs to establish, maintain, expand, enforce and defend the scope of our

intellectual property portfolio, including the amount and timing of any

payments we may be required to make, or that we may receive, in connection with

licensing, preparing, filing, prosecuting, defending and enforcing our patents

or other intellectual property rights;

? expenses incurred to attract, hire and retain skilled personnel;

? the costs of operating as a public company; and

? the impact of the COVID-19 pandemic, which may exacerbate the magnitude of the

10,752

Cash Flows Used in Operating Activities

Net cash used in operating activities was $14.2 million and $6.2 million for thethree months ended March 2022 and 2021, respectively.

Cash Flows Used in Investing Activities

Cash Flows from Financing Activities

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JASPER THERAPEUTICS, INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) - Marketscreener.com

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Aileron Therapeutics, Inc.

Taxanes, such as paclitaxel and docetaxel, cause severe and often permanent chemotherapy-induced hair loss (alopecia)

New non-clinical data demonstrate proof of principle that ALRN-6924 can temporarily arrest the cell cycle in human scalp hair follicles and their stem cells

ALRN-6924-induced cell cycle arrest protected hair follicles from paclitaxel-induced toxicity and irreversible stem cell damage

Ailerons precision medicine-based approach is designed to selectively protect normal, healthy cells from chemotherapy while ensuring chemotherapy cannot protect cancer cells

Ailerons ongoing non-small cell lung cancer (NSCLC) clinical trial and upcoming breast cancer clinical trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities and other side effects, including alopecia

BOSTON, May 10, 2022 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives, today announced a late-breaking oral presentation at the upcoming Society for Investigative Dermatology (SID) Annual Meeting, which will be held May 18 21, 2022 in Portland, Oregon. The presentation will highlight new non-clinical data developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues at the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery at the University of Miami Miller School of Medicine. This collaboration has generated promising ex vivo data demonstrating that ALRN-6924 protected human hair follicles and their stem cells from chemotherapy-induced acute and permanent damage. Details of the presentation are as follows:

Title:

ALRN-6924, a dual inhibitor of MDMX and MDM2, protects human scalp hair follicles and their epithelial stem cells from paclitaxel-induced toxicity (LB1018)

Presenter:

Jennifer Gherardini, Ph.D.; Paus Laboratory, University of Miami Miller School of Medicine

Date:

Thursday, May 19th

Time:

8:45 AM 11:15 AM PT

Session:

Late-Breaking Abstract Concurrent Session

Chemotherapy-induced toxicities range from severe and life-threatening to those that impact and diminish patients quality of life, sometimes long after chemotherapy has been completed. These toxicities occur because chemotherapy destroys normal, healthy cells while simultaneously destroying cancer cells, said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. Previously, we showed chemoprotection against severe bone marrow toxicities in small cell lung cancer patients receiving topotecan and demonstrated in healthy volunteers the mechanism of action cell cycle arrest underlying this chemoprotection benefit. We are excited to now present new data that may suggest ALRN-6924s ability to also protect against chemotherapy-induced hair loss, another devastating chemotherapy-induced side effect for millions of cancer patients.

Dr. Paus commented, These results got us quite excited as they directly follow in the footsteps of our prior work that showed arresting the cell cycle can have a strong protective effect against taxane-induced hair follicle damage. Until our research with ALRN-6924, we had not come across a cell cycle arrest-inducing drug that is in clinical testing for protection of normal cells without protecting cancer cells. Thus, ALRN-6924 invites a very promising and completely novel selective protection approach. In addition, we found that ALRN-6924 may exert some additional benefits that could reduce the risk of long-term damage of human hair follicle stem cells by taxanes.

Story continues

Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapys attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells. The companys vision is to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy.

About the Findings

Taxanes, such as paclitaxel and docetaxel, are known to cause severe and often permanent chemotherapy-induced alopecia. Over 90% of patients treated with this chemotherapy class experience alopecia, and approximately 10% (paclitaxel) to 25% (docetaxel) of patients experience permanent alopecia. Dr. Paus and his team previously demonstrated that paclitaxel damages human scalp hair follicles by inducing massive mitotic defects and apoptosis in hair matrix keratinocytes as well as bulge stem cell DNA damage, and that pharmacological induction of transient cell cycle arrest can protect hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron previously conducted in vitro studies showing that ALRN-6924 protected human fibroblasts in cell culture from multiple chemotherapies, but not p53-mutant breast cancer cells.

In the new non-clinical findings to be presented at the SID meeting, when organ-cultured anagen (i.e., active growth phase) scalp hair follicles from two human donors were pre-treated with ALRN-6924 or vehicle (i.e., placebo), followed by paclitaxel or vehicle, ALRN-6924 significantly increased the number of p21-positive hair matrix keratinocytes and bulge stem cells compared to vehicle or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a reduction in the number of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, as well as a reduction in apoptosis, pathological mitosis, and DNA damage. Aileron believes that these findings support clinical investigation of ALRN-6924 to prevent both acute and permanent chemotherapy-induced alopecia, in addition to its ongoing evaluation of ALRN-6924 to protect against chemotherapy-induced bone marrow and other toxicities.

About Ailerons Clinical Trials of ALRN-6924

Aileron is on track to initiate a Phase 1b randomized, controlled trial of ALRN-6924 in patients with p53-mutated ER+/HER2- neoadjuvant breast cancer in 2Q 2022. The planned breast cancer trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities, as well as other toxicities, including alopecia, in patients with p53-mutated ER+/HER2- breast cancer treated with a doxorubicin plus cyclophosphamide and docetaxel chemotherapy regimen.

The company is currently enrolling patients in a Phase 1b randomized, double-blind, placebo-controlled trial evaluating ALRN-6924s protection against chemotherapy-induced bone marrow and other toxicities in patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. While patients in this trial are monitored for alopecia, historically, only a small percentage of patients treated with carboplatin plus pemetrexed experience acute alopecia. Aileron is on track to report interim results on the first 20 patients enrolled in the NSCLC trial in June 2022 and topline results on 60 patients in 4Q 2022.

About Aileron Therapeutics

Aileron is a clinical stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.

Our vision is to bring chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.

Forward-Looking Statements

Statements in this press release about Ailerons future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective agent, including its ability to prevent both acute and permanent chemotherapy-induced alopecia, and the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether initial results of clinical trials will be indicative of final results of those trials or results obtained in future clinical trials, including trials in different indications; whether ALRN-6924 will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will be accepted by and warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive approval from regulatory agencies on a timely basis or at all or in which territories or indications ALRN-6924 may receive approval; whether, if ALRN-6924 obtains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on the timing of our clinical development, clinical supply and our operations; and other factors discussed in the Risk Factors section of Ailerons annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Investor Contact:Stern Investor RelationsAlexander Loboalex.lobo@sternir.com

Media Contact:Liz Melone617-256-6622

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Aileron Therapeutics Announces Late-Breaking Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their...

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SAN DIEGO, Calif., SUZHOU and SHANGHAI, China , May 12, 2022 /PRNewswire/ -- Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, today announced the details of three abstracts that it will present at the European Hematology Association 2022 Hybrid Congress (EHA2022 Congress), being held from June 9 June 12 in Vienna, Austria. The abstracts highlight the clinical data from ongoing investigator-initiated trials (IITs) of BCMA/CD19 dual-targeting FasTCAR candidate GC012F in two indications of B-cell non-hodgkin's lymphoma (B-NHL) and relapsed/refractory multiple myeloma (RRMM), and allogeneic TruUCAR candidate GC502 in B-cell acute lymphoblastic leukemia (B-ALL).

"We are very excited to share our data for both our FasTCAR candidate GC012F in two indications of RRMM and B-NHL, and allogeneic TruUCAR candidate GC502 in B-ALL at the EHA2022 Congress," said Dr. Martina Sersch, Chief Medical Officer of Gracell. "The new data, including the expanded indication of GC012F into B-NHL, demonstrates the potential of our platforms and provides further validation. The clinical data of BCMA/CD19 dual-targeting GC012F in the treatment of B-NHL shows promising early results, along with benefits of the next-day manufacturing enabled by the FasTCAR platform. The CD19/CD7 dual-directed CAR-T therapy GC502 is our second allogeneic candidate on our TruUCAR platform, demonstrating the potential wide applicability of the TruUCAR design."

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of B-NHL

GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19. It is developed using Gracell's proprietary FasTCAR platform which enables next-day manufacturing, and is currently being evaluated in IITs in China including in RRMM and B-NHL. GC012F is the first BCMA/CD19 dual-targeting CAR-T in human trials for B-NHL.

Gracell will present the early results of the first-in-human phase 1 IIT in China evaluating the safety and tolerability of GC012F in B-NHL patients. Three patients who had received a median of two prior lines of therapy were enrolled, all of which presented with bulky disease. As of the February 22, 2022 data cutoff date, the enrolled patients had received one single infusion of GC012F at three different doses of 3.7x104 cells/kg and 2-3x105 cells/kg.

All three patients had achieved a complete response (CR) confirmed by PET- CT at day 28 after GC012F infusion. At 3-month follow-up, both of the two assessable patients had ongoing response. No dose-limiting toxicities were observed and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. CRS presented as Grade 1 in two patients and Grade 3 in one patient (duration of two days) with no Grade 4 or 5 events.

Details of the presentation are as follows:

BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of RRMM

Gracell will also present as an oral abstract presentation the updated results from the first-in-human IIT evaluating GC012F for the treatment of RRMM patients. This data is currently under embargo and will be published on the EHA2022 Hybrid Congress website on Thursday, May 26 concurrently with ASCO.

Details of the presentation are as follows:

CD19/CD7 Dual-directed Allogeneic TruUCAR-T GC502 for the Treatment of B-ALL

GC502 leverages the novel dual-directed CAR design of Gracell's proprietary TruUCAR platform, designed to generate high-quality allogeneic CAR-T cell therapies that can be administered "off-the-shelf" at lower cost and with faster patient's access. TruUCAR-enabled GC502 utilizes the dual-directed CAR design with one CAR targeting CD19 on malignant cells and a second CAR targeting CD7 to suppress host-versus-graft rejection. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells.

Between September 2021 and January 2022, four r/r B-ALL patients were enrolled and treated in an open-label, non-randomized, prospective IIT in China in two different dose levels and with two different formulations. Patients were heavily pretreated, and all had previously received either autologous or donor derived CD19 or CD19/CD22 targeted CAR-T therapy. As of the January 28, 2022 data cutoff date, all four patients had received a single dose of GC502, including one patient at dose level 1 (DL1) 1.0x107 cells/kg and three patients at dose level 2 (DL2) 1.5x107 cells/kg. Patients received a Flu/Cy based lymphodepletion regimen prior to treatment with GC502.

Three of four patients achieved minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi), and one patient achieved a partial response at month one and subsequently received allogeneic hematopoietic stem-cell transplantation (allo-HSCT) on day 39.

Cytokine release syndrome (CRS) presented as Grade 2 and Grade 3 with no Grade 4 or 5 events. No immune effector cell-associated neurotoxicity syndrome (ICANS) or acute graft-versus-host disease (aGvHD) were observed.

Details of the presentation are as follows:

For more information about the EHA2022 Hybrid Congress, visit http://www.ehaweb.org.

About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin's lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About B-NHL

Non-Hodgkin's lymphoma (NHL) is a group of blood cancers that developed from lymphocytes, most commonly derived from B cells (B-NHL). Globally, approximately 510,000 patients are diagnosed with NHL every year with about 80,470 patients expected to be diagnosed with NHL in the United States in 2022[1]. B-NHL accounts for approximately 85% of NHL diagnoses.

[1] Data source: American Cancer Society

About GC502

GC502 is a TruUCAR-enabled CD19/CD7 dual-directed, off-the-shelf allogeneic CAR-T product candidate that is being studied in an ongoing Phase 1 IIT in China for the treatment of B-cell malignancies. GC502 is manufactured using T cells from non-human leukocyte antigen (HLA) matched healthy donors. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells. Optimized for CD19/CD7 dual-CAR functionality and in vivo durability, GC502 has demonstrated robust anti-tumor effects with potential to suppress host versus graft (HvG) rejection in preclinical models.

About B-ALL

Acute lymphoblastic leukemia (ALL) is a type of blood cancer characterized by proliferation of immature lymphocytes in the bone marrow, which can involve either T lymphocytes (T-ALL), or B lymphocytes (B-ALL). Globally, approximately 64,000 patients are diagnosed with ALL every year with an estimated 6,660 new cases to be diagnosed in the United States in 2022[2]. B-ALL accounts for 75% of ALL diagnoses in adults.

[2] Data source: American Cancer Society

About FasTCAR

CAR-T cells manufactured on Gracell's proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.

About TruUCAR

TruUCAR is Gracell's proprietary technology platform and is designed to generate CAR-T cell therapies from high quality allogeneic T cells that can be administered "off-the-shelf" at lower cost and with improved accessibility of cell therapies for cancer patients. With differentiated design enabled by gene editing, TruUCAR is designed to control HvG as well as GvHD without the need for being co-administered with additional strong immunosuppressant after conventional lymphodepletion. The novel dual-CAR design allows tumor antigen-CAR moiety to target malignant cells, while the CD7 CAR moiety is designed to suppress rejection (HvG response) of allogeneic CAR-T cells by host T and NK cells (HvG).

About Gracell

Gracell Biotechnologies Inc.("Gracell") is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CARTMtechnology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost, and lack of effective CAR-T therapies for solid tumors. For more information on Gracell, please visit http://www.gracellbio.com.Follow @GracellBio on LinkedIn.

Cautionary Noted Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the expected trading commencement and closing date of the offering. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the section entitled "Risk Factors" in Gracell's most recent annual report on Form 20-F as well as discussions of potential risks, uncertainties, and other important factors in Gracell's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Gracell specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon the information on this page as current or accurate after its publication date.

Media contacts

Marvin Tang[emailprotected]

Kyle Evans[emailprotected]

Investor contacts

Gracie Tong[emailprotected]

Stephanie Carringtonsteph[emailprotected]

SOURCE Gracell Biotechnologies Inc.

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Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic...

Bone Marrow Stem Cells Comments Off on Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic… | May 13th, 2022

Paper Title: Identification of a retinoic acid-dependent hemogenic endothelial progenitor from human pluripotent stem cells

Journal: Nature Cell Biology

Authors:Christopher Sturgeon, PhD, Associate Professor of Cell, Developmental & Regenerative Biology and Medicine, Hematology & Medical Oncology in the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, and other coauthors.

Bottom Line:Blood-forming stem cells found in bone marrow are the life-saving component used in bone marrow transplants. However, suitable donors often cannot be found in many cases. This study reveals how the human embryo develops the precursor to blood forming stem cells, which researchers say can be used in the novel method they developed to generate blood-forming stem cells from cells in tissue culture.

The studyled by researchers from Mount Sinai and the San Raffaele Telethon Institute for Gene Therapy in Milan Italyconfirms many aspects of cell development, including origins and regulation, which are known to occur within both the mouse and human embryo. In the mammalian embryo, blood-forming stem cells emerge from a specialized cell type called hemogenic endothelium. These cells develop in response to a critical signal pathway known as retinoic acid, which is essential for growth. Their analysis found that stem cell populations derived from human pluripotent stem cells were transcriptionally similar to cells in the early human embryo.

Results: For years, researchers in the field of regenerative medicine have been able to obtain hemogenic endothelium from embryonic stem cells, but these cells do not produce blood-forming stem cells. In the embryo, blood-forming stem cell development requires signaling by retinoic acid.But, current state-of-the-art methods for deriving blood progenitors from human pluripotent stem cells do so in the absence of retinoic acid. In this latest study, researchers examined the dependence on retinoic acid in early cell types derived from human pluripotent stem cells. They performed single cell RNA sequencing of stem cells in vitro to better understand patterns of mesodermal cell types during early development. The research team identified a new strategy to obtain cells that are transcriptionally similar to those hemogenic endothelial cells found in the human embryo by stimulating a very discrete original population with retinoic acid.

Why the Research Is Interesting:This new method brings researchers and scientists closer to developing blood-forming stem cells in tissue culture, but also provides a pathway to establishing specialized blood cell types for transfusions and other treatments for cancer since the new method makings it possible to obtain the same original cells in adult blood that are found in a developing embryo.

Said Mount Sinai's Dr. Christopher Sturgeon of the research:We have made a major breakthrough in our ability to direct the development of stem cells in a tissue culture dish into cells that have the same gene expression signature as the immediate progenitor of a blood-forming stem cell found in the developing embryo. With this, now we can focus our efforts at understanding how to capture embryonic blood-forming stem cells, with the goal of using them as a substitute for bone marrow.

Researchers from the Washington University School of Medicine in St. Louis, MO contributed to this study.

###

To request a full copy of the paper or to schedule an interview with the researcher, please contact the Mount Sinai Press Office at stacy.anderson@mountsinai.org or 347-346-3390.

Nature Cell Biology

28-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -...

Bone Marrow Stem Cells Comments Off on Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -… | April 29th, 2022

There are few things more grueling than running a marathon.

One of those is battling cancer.

A La Conner native knows all about the former, having previously run the Denver Colfax Marathon. Now shes helping bring greater awareness to the latter by raising funds for the Leukemia & Lymphoma Society as she trains for the Chicago Marathon in October.

Morgan Harlan, a 2020 Baylor University grad now teaching kindergarten in Denver, is hoping to raise $4,000 for LLS by running the urban Chicago course with two friends this fall. The Chicago Marathon is typically viewed by more than a million spectators.

I hope to raise as much money as I possibly can for such a worthy cause that is so important to my family, she told the Weekly News on Friday.

Her family has seen first-hand the life-saving potential of bone marrow and blood stem cell transplants, and is committed to helping find cures and ensure access to treatments for all blood cancer patients.

Harlans grandfather, longtime La Conner resident and Dunlap Towing retiree Mit Harlan, waged a successful battle against leukemia over a decade ago.

My grandfather, said Harlan, is alive because of a stem cell transplant.

While a student at Baylor, where she was a journalism/public relations major and played club soccer, Harlan signed up for Be the Match, which connects patients with transplant donors.

As a college student with a family member who had experienced cancer, said Harlan, I thought I was doing my due diligence by signing up for the registry.

Last December, four years after joining Be the Match, Harlan flew to Seattle to donate her stem cells.

Her patient was a 65-year-old male with leukemia the same age her grandfather was when he received his transplant.

When Be the Match called to inform me that I was the match and asked me if I would be willing to donate my stem cells, Harlan added, my response was: Absolutely. I hope I can give another little girl or boy more time with their grandpa like I was given.

Harlan has not stopped there. She has taken on fundraising for the cause, doing so in a way that shows she is in it for the long run.

She has enlisted a coach, La Conner alum Carlee Daub, to help her train for Chicago. Daub is an owner of Wahoo Running, an online platform that provides coaching to runners throughout the nation.

My first marathon, Harlan recalled, I was focused on completion. I wanted to prove to myself that I had the physical and mental grit to get through 26.2 miles. The Chicago Marathon will be focused more on speed and race strategy.

As Harlan has lowered her running times, her fundraising numbers have increased.

My fundraising has gone really well because of the wonderful people around me, she said. I am very thankful to have generous family members, friends, and community members.

My original goal was to raise $2,000, Harlan explained, which I was able to raise in the first week. I have since raised my goal to $4,000.

Committing to run the Chicago Marathon on behalf of LLS is a big step for Harlan. After graduating from Burlington-Edison High School, having competed in soccer and track there, Harlan chose to go out of state for college.

I wanted to travel outside of Washington for my four years of college and live somewhere new, she said. Baylor had a great mix of academic strength, athletics success and extracurriculars.

While on the Waco, Texas campus, Harlan regularly wrote for the student newspaper, the Baylor Lariat.

Now, as she preps for the Chicago Marathon and generates support for LLS, Harlan is making rather than reporting the news.

For her, its a story whose headliner is her grandfather.

Hes one of the best humans I know, said Harlan. Growing up, he never missed a soccer match (of mine), including a tournament in Spain. Hes very giving with his time and money, especially towards charities like LLS.

Harlan, daughter of Mike and Jennifer Harlan, of Landing Road, southeast of La Conner, said the best ways to donate are through either her donation page: (https://pages.lls.org.tnt/rm.chicago22/MHarlan) or Facebook.

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La Conner native raising funds to cure blood cancer - La Conner Weekly News

Bone Marrow Stem Cells Comments Off on La Conner native raising funds to cure blood cancer – La Conner Weekly News | April 29th, 2022

Community members are speaking out about the role blood donation has played in their personal lives.

This comes as Action News Jax and our Family Focus partners have teamed up for our annual Spring Into Action Blood Drive.

Jacksonville resident Penelope McGowan told Action News Jax reporter Kennedy Dendy that having the opportunity to give blood is an honor. My father needed a life-saving procedure, so it became more important to me to start giving blood, McGowan said.

She then became a regular giver, knowing the impact donation truly has.

That allowed him the time to spend time with his grandchildren, McGowan said. He walked his granddaughter down the aisle and got to see some of his great-grandchildren.

McGowan said blood donation made that moment possible.

Now that hes passed away, I want to give that gift of time to other families, McGowan said. So, its so important to me to give blood.

RELATED: OneBlood, Action News Jax team up for the Spring into Action Blood Drive

Action News Jax also spoke with John Dean, who is a patient at the Mayo Clinic. Hes from South Carolina but has been living in Jacksonville since January.

I got the bone marrow transplant, which is basically a stem cell infusion on January 17th, Dean said. I have been dealing with myelodysplastic syndrome.

Dean said its a form of bone marrow cancer hes been battling since 2017.

During that time, I had become increasingly dependent upon blood because the syndrome destroys my bodys ability to make red blood cells, Dean said. So when the blood numbers drop, I get very very sick.

He said the transplant was designed to cut down on his need to get the blood, but that hasnt happened yet.

Ive been more blood dependent since January than I had been before I came down here, Dean said.

Dean spoke with me just moments after he received a blood transfusion at the hospital -- but he wanted one message out there.

Youre transmitting a miracle, Dean said. Im a living example of that. I would not be here were it not for the blood.

Story continues

OneBlood said to donate youll need an ID, and you must be 16 years and older.

Randy Varner donated double red blood cells at Tuesdays drive.

My wife has had to have two heart valves replaced, so shes had to have blood before at the hospital -- so I try to help out when I can, Varner said.

Varner shared that if youre able to -- you should give.

Theres nothing to it, Varner said. You go in there. You answer a few questions. You lay down. You can take a little nap if you have to.

Nicole Payne is the Senior Program and Membership Director with the Brooks Family YMCA, one of the many sites for the drive.

Theres always a lack of blood available for people that come into any traumatic situation, Payne said. We want to make sure that we can hopefully combine some of the best parts of Jacksonville -- and thats through OneBlood being here to help people have access to donate.

The Spring into Action Blood Drive kicked off Tuesday and runs through Friday.

When you donate you will receive a free t-shirt, a $20 e-gift card, and an additional gift depending on the location where you donate.

CLICK HERE to find out when and where you can donate.

STAY UPDATED: Download the Action News Jax app for live updates on breaking stories

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I would not be here were it not for the blood: Duval residents describe impact of blood donation - Yahoo News

Bone Marrow Stem Cells Comments Off on I would not be here were it not for the blood: Duval residents describe impact of blood donation – Yahoo News | April 29th, 2022

REGULATED INFORMATION

Strategic focus revised and fully focused on achieving topline results of the ALLOB Phase IIb study in tibial fractures.

Discussions for ALLOB global partnership still ongoing.

Board of Directors and Management exploring all strategic options to protect shareholder value.

Strengthening financial position with EIB agreement and private placement in 2021 and a new bond issuance foreseen in May 2022

Management to host conference call today at 3pm CEST / 9am EST - details provided below

Mont-Saint-Guibert, Belgium, 29April 2022, 7am CEST BONE THERAPEUTICS (Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today announces its business update and full year financial results for the year ending 31 December 2021, prepared in accordance with IFRS as adopted by the European Union.

Incomplete fracture healing remains a seriously unmet medical need affecting hundreds of thousands of patients worldwide. Despite the pandemic and subsequent seriously geopolitical and economic global events, Bone Therapeutics still remains on target for delivery of topline results for its Phase IIb study of its allogeneic cell therapy product, ALLOB, in patients with difficult tibial fractures, said Miguel Forte, MD, PhD, CEO of Bone Therapeutics. We believe ALLOB could provide difficult tibial fracture patients a convenient treatment option with a potentially superior outcome. Having successfully completed two clinical studies showing promising safety profile and efficacy signals in more than 60 patients, we firmly believe that ALLOB has the highest potential of near-term value creation and is focused on completing the current Phase IIb study. In addition, Bone Therapeutics has made a serious contribution for the future into the use of Induced Pluripotent Stem Cell (iPSC) derived, genetically engineered MSCs. Bone Therapeutics is continuing its efforts to establish value adding business collaborations and to strengthen its financial position.

Clinical and operational highlights (including post-period events)

In January 2021, Bone Therapeutics initiated the treatment of patients in the Phase IIb study of its allogeneic cell therapy product, ALLOB, in patients with difficult tibial fractures. Bone Therapeutics anticipates finalizing patient recruitment of this study in 2022. This recruitment finalization is subject, as across the industry, to evolution of the ongoing COVID-19 pandemic and the associated containment measures. Although early recruitment rates were very promising, the recruitment rates have temporarily slowed in subsequent months due to pandemic-related factors, such as reduced site activities due to staff availability and the number of available patients due to less occurrence of accidents. Bone Therapeutics has implemented several mitigating measures in collaboration with the involved clinical research organization to improve and facilitate recruitment. These measures include site expansion, training, information, best practices sharing and close monitoring of progress. As a result of these measures and the improving recruitment rate, Bone Therapeutics continues to currently expect the release of topline data by Q1 2023.

In January 2021, Bone Therapeutics signed an initial agreement for a process development partnership with the mesenchymal stromal cell (MSC) specialist, Rigenerand. This collaboration focused on further developing and enhancing Bone Therapeutics bone-forming platform.

In June 2021, Bone Therapeutics published the positive results of its Phase I/IIa clinical trial with ALLOB in patients with delayed union fractures. The results were published in Stem Cell Research & Therapy, the international peer-reviewed journal focusing on translational research in stem cell therapies. ALLOB was generally well-tolerated and that all patients met the primary endpoint.

In August 2021, Bone Therapeutics announced topline results from the Phase III knee osteoarthritis study with its enhanced viscosupplement JTA-004, its legacy non-MSC product. JTA-004 had a favorable safety profile. However, the study did not meet the primary and key secondary endpoints. No statistically significant difference in pain reduction could be observed between the treatment, placebo and comparator groups, with all treatment arms showing similar efficacy.

In September 2021, Bone Therapeutics signed a research evaluation agreement with Implant Therapeutics, the developer of hypoimmunogenic and safe harbor engineered IPSC derived cells. The agreement enables Bone Therapeutics to access, evaluate and materially transfer Implant Therapeutics Induced Pluripotent Stem Cell (iPSC) derived, genetically engineered MSCs, including lines, media, differentiation protocols and expertise.

In November 2021, Bone Therapeutics signed a non-binding term sheet for the global rights for ALLOB, Bone Therapeutics allogeneic osteoblastic cell therapy product, with one of its current Chinese partners, Link Health Pharma Co., Ltd (Link Health). The negotiations for the global rights agreement are still ongoing but take longer than expected. The envisaged completion of a final binding agreement has been delayed and is now contemplated over the course of Q2 2022.

Corporate highlights (including post-period events)

In March, 2021, Bone Therapeutics appointed the stem cell therapy industry veteran, Anthony Ting, PhD, as Chief Scientific Officer. Dr. Ting is responsible for Bone Therapeutics research activities.

In July 2021, Bone Therapeutics appointed Dr. Anne Leselbaum as Chief Medical Officer. Dr. Leselbaum brings three decades of experience in strategic international clinical development, clinical operations and medical affairs. As CMO, she takes responsibility for the leadership of all clinical development and medical affairs strategies and activities across the entire Bone Therapeutics pipeline and will oversee the regulatory interactions.

In September 2021, Bone Therapeutics appointed Lieve Creten, as interim Chief Financial Officer (CFO), succeeding Jean-Luc Vandebroek. Lieves extensive financial experience ensures the continued optimal financial control, oversight and compliance.

In October 2021, Bone Therapeutics appointed key experts to its Scientific Advisory Board (SAB). The members of the SAB consist of world-recognized scientists and clinicians in the cell and gene therapy field.

In March 2022, Bone Therapeutics announced it was redefining its strategic priorities to concentrate specifically on the development of its most advanced clinical asset, ALLOB. As a result, Bone Therapeutics will focus its R&D activities to support the clinical development of ALLOB and all activities related to the development of the pre-clinical iMSCg platform as well as all other non ALLOB related activities, were stopped. In this context, some members of Bone Therapeutics' management team will depart Bone Therapeutics in the following months in alignment with the refocus in activity. This includes Miguel Forte (CEO), Tony Ting (CSO), Stefanos Theoharis (CBO) and Lieve Creten (CFO). During the transition, CEO, Miguel Forte, will remain in function. The Scientific Advisory Board was also dissolved.

Financial highlights (including post-period events)

In July 2021, Bone Therapeutics secured a loan agreement of up to 16.0 million with the European Investment Bank (EIB). The EIB loan financing will be disbursed in two tranches of 8.0 million each, subject to conditions precedent. Following the approval of the issuance of associated warrants by Bone Therapeutics General Meetings at the end of August 2021, Bone Therapeutics received a payment from the EIB for the first tranche of 8.0 million and the EIB was granted 800,000 warrants approved by the Extraordinary General Meeting.

In August 2021, Bone Therapeutics also renegotiated 800 convertible bonds issued on May 7, 2020 (for an amount of 2 million) to Patronale Life into a loan subject to the same repayment terms as the agreement with the EIB, with the issuance of 200,000 additional warrants approved by the Extraordinary General Meeting.

In December 2021, Bone Therapeutics raised additional 3.3 million funding through a private placement with current and new institutional investors to advance its lead orthopedic asset, ALLOB, through mid-stage clinical development.

The total revenues and operating income for 2021 amounted to 2.7 million compared to 3.7 million in 2020. As a result of the reduced clinical activities following the completion of the Phase III JTA-004 study, and the slower pace of patient enrollment for the ALLOB TF2 Phase IIb study due to the COVID-19 pandemic, operating loss for the period decreased to 12.0 million from 15.0 million for the full year 2020. Consequently, cash used for operating activities amounted to 12.8 million for the full year 2021. Year-end cash position amount to 9.5 million compared to 14.7 million year-end 2020.

In April 2022, Bone Therapeutics signed a binding term sheet for a 5 million convertible bonds (CBs) facility arranged by ABO Securities. The proceeds of the financing will be used to advance the clinical development of Bone Therapeutics lead asset, the allogeneic bone cell therapy, ALLOB. ABO Securities, on behalf of the CB investor, commits to subscribe to up to 5 million in CBs. Subject to the fulfillment of condition precedents, Bone Therapeutics and ABO Securities aim to agree on and execute the final subscription agreement for the CBs and to issue the first tranche of CBs by the beginning of May 2022.

Outlook for the remainder of 2022

In the ongoing Phase IIb ALLOB clinical study in difficult tibial fractures, Bone Therapeutics clinical team, in partnership with its clinical research organization, is continuing to institute measures to mitigate the impact of the pandemic and will closely monitor the recruitment progress. As a result of the initial mitigation actions and the improving recruitment rate due to the gradual lifting of COVID-19 related measures in Europe, Bone Therapeutics expects to report topline results as scheduled by the first quarter of 2023. However, a delay cannot be excluded. Should the pandemic continue to have impact on patient availability, Bone Therapeutics may have to re-evaluate this timeline and, in that eventuality, will communicate again to the market.

The negotiations for ALLOB, with one of Bone Therapeutics current Chinese partners, for the global rights agreement are still ongoing but are taking longer than originally anticipated. The potential completion of a final binding agreement has been delayed into Q2 2022.

Subsequent to some preliminary contacts, the board of directors of Bone Therapeutics is currently examining various opportunities to combine certain activities within Bone Therapeutics, taking into account the interests of its shareholders and other stakeholders. Further announcements will be made in due course, if and when circumstances so allow or require.

Following the restructuring of the management team announced on 12 April 2022, Bone Therapeutics has initiated the search for a new CEO and CFO.

Disciplined cost and cash management will remain a key priority. The operating cash burn for the full year 2022 is expected to be in the range of 8-10 million, assuming normal operations as the effect of the ongoing COVID-19 epidemic cannot be excluded. The situation will be actively and closely monitored. The company anticipates having sufficient cash to carry out its business objectives into Q1 2023, assuming, amongst other, full issuance of the new convertible bond facility. Bone Therapeutics refers to the going concern statement in the Annual Report 2021 for all key assumptions taken.

Conference call

Miguel Forte, MD, PhD, Chief Executive Officer will host a webcast with conference call today at 3:00 pm CEST / 9:00am EST. To participate in webcast or the conference call, please use the following link:

https://us06web.zoom.us/j/81633950602

Or select your dial-in number from the list below quoting the conference ID 816 3395 0602#:

Belgium: +32 2 290 9360France: +33 1 7095 0103United Kingdom: +44 208 080 6592United States: +1 646 876 9923

The presentation will be made available on the Investors section - Presentations of the Bone Therapeutics website shortly prior to the call.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and other diseases. Currently Bone Therapeutics is concentrating specifically on the development of its most advanced clinical asset, the allogeneic cell therapy platform, ALLOB.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell and gene therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Its leading investigational medicinal product, ALLOB, represents a unique, proprietary approach to bone regeneration, which turns undifferentiated stromal cells from healthy donors into bone-forming cells. These cells are produced via the Bone Therapeutics scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, the Company has initiated patient recruitment for the Phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB continues to be evaluated for other orthopedic indications including spinal fusion, osteotomy, maxillofacial and dental.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the Louvain-la-Neuve Science Park in Mont-Saint-Guibert, Belgium. Further information is available at http://www.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerLieve Creten, Chief Financial Officer ad interimTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicBert BouserieTel: +32 (0)488 40 44 77bert.bouserie@bepublicgroup.be

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: +33 (0)1 44 71 94 94bone@newcap.eu

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

Excerpt from:
Bone Therapeutics announces 2021 full year results - GlobeNewswire

Bone Marrow Stem Cells Comments Off on Bone Therapeutics announces 2021 full year results – GlobeNewswire | April 29th, 2022

Early outcomes with the combination of JSP191, fludarabine, and low-dose total body radiation (TBI) demonstrated facilitation of full donor myeloid chimerism, clearing of minimal residual disease (MRD), and a well-tolerated safety profile in older patients with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) receiving non-myeloablative (NMA) allogenic hematopoietic cell transplantation (AHCT).

Results from the phase 1 trial (NCT04429191) presented at the 2022 Transplantation & Cellular Therapy Meetings, showed there were no infusion toxicities or serious adverse events with JSP191, and no instances of primary graft failure in first 24 patients enrolled on the trial; only 1 patient had secondary graft failure and went on to have successful retransplant. Additionally, MRD clearance was observed in 12 patients, and JSP191 pharmacokinetics were shown to be predictable.

AHCT is the only curative treatment for many patients with MDS/AML, even though there have been advancements in therapy for these patients in recent years. While transplant has proven feasible for adults well into their 70s, the optimal conditioning regimen for older adults remains unknown as more intensive regimens tend to be associated with transplant-related mortality, while less intensive nonmyeloablative regimens have resulted historically in higher rates of disease relapse and progression, Lori Muffly, MD, MS, said in her presentation.

Therefore, a conditioning regimen that results in minimal toxicity but has enhanced disease control is needed in order to improve transplantation outcomes in this population, Muffly, associate professor of medicine (blood and marrow transplantation and cellular therapy) at Stanford Healthcare, continued.

JSP191 is a humanized monoclonal antibody meant to block stem cell factor binding site on CD117, which is necessary for hematopoietic stem cell (HSC) survival and HSC interactions in the bone marrow niche. After the bone marrow niche is emptied because of JSP191 binding to CD117, healthy donor cells are able to engraft. Preclinical models showed synergy between anti-CD117 monoclonal antibodies and low-dose TBI to help deplete HSC and facilitate donor cell engraftment.

For the first 24 patients with MDS (n = 13) or AML (n = 11), primary end points evaluated were safety, tolerability, and pharmacokinetics of the combination. Secondary end points included engraftment and donor chimerism, MRD clearance, relapse-free survival, graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Patients received AHCT, then 200 to 300 cGy of TBI, 30 mg/m2 of fludarabine for 3 days, and 0.6 mg/kg of intravenous JSP191.

To determine the starting date of fludarabine, real-time pharmacokinetic measurements and modeling were used after JSP191 was administered. For the first 7 patients, TBI was increased from 200 to 300 cGy to aid lymphoablation. Tacrolimus, sirolimus, and mycohphenolate motefil were used as GVHD prophylaxis.

Consistent pharmacokinetics and predictable clearance were observed with JSP191 over the 2 weeks after administration. All patients were able to receive donor cell infusion between 9 and 15 days following administration of the antibody. Interestingly, we did see in some patients very low levels of the antibody present on the day of donor cell infusion, and this did not appear to impact donor cell engraftment, Muffly said.

Bone marrow aspirations taken at screening and between administration of the antibody and fludarabine/TBI showed JSP191 depletes hemopoietic stem and progenitor cells (HSPC). In the CD34-positive, CD45RA-negative population, there was a 66% mean depletion of HSPC. The investigators do not believe this reflects the nadir of HSPC depletion, Muffly explained, and that the depletion continues until donor stem cell infusion.

All patients experienced neutropenia followed by neutrophil engraftment between TD+15 and TD+26. Primary engraftment was seen in all patients, with only 1 patient losing myeloid chimerism early, which was associated with disease progression. T cell chimerism improved when patients went up from 200 to 300 cGy.

Using flow cytometry, cytogenetics, and next-generation sequencing, investigators were able to track MRD in patients with de novo AML (n = 8) and AML from MDS (n = 3). Of the 9 patients with AML who were MRD positive at the time of enrollment, 6 were MRD negative at the time of follow-up. Eleven of 13 patients with MDS were MRD positive at enrollment, and 8 were MRD negative at the last follow-up.

After 6 months median follow-up (range, 2-12 months), there were no reports of classical grade II-IV acute GVHD. One case of late onset grade III-IV acute gastrointestinal GVHD was reported as of the latest follow-up, but this patient had non-relapse mortality. Any instances of chronic GVHD has yet to be reported due to insufficient median follow-up time. Morphologic relapse occurred in 4 patients, 3 with AML and 1 with MDS.

The median age for these patients was 70 years (range, 62-79), with a requirement of 60 years of age or older or an AHCT-comorbidity index of 3 or more to enroll in the trial. They could not have prior AHCT and needed a human leukocyte antigenmatched related or unrelated donor. Over half of patients received only a hypomethylating agent-containing regimens.

JSP191 in combination with fludarabine and low-dose TBI is a novel conditioning platform that appears safe, well tolerated, has demonstrated on-target effects of HSPC depletion, permits full donor myeloid chimerism, and results in promising early MRD clearance, Muffly concluded.

Reference:

Muffly L, Lee CJ, Gandhi A, et al. Preliminary data from a phase 1 study of JSP191, an anti-CD117 monoclonal antibody, in combination with low dose irradiation and fludarabine conditioning is well-tolerated, facilitates chimerism and clearance of minimal residual disease in older adults with MDS/AML undergoing allogeneic HCT. Presented at: 2022 Transplantation & Cellular Therapy Meetings; Salt Lake City, UT; April 23-26, 2022. Abstract LBA4. https://bit.ly/3xRTwee

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Interim Data Targeting CD117 Show Promising MRD Results and Safety in MDS/AML - Targeted Oncology

Bone Marrow Stem Cells Comments Off on Interim Data Targeting CD117 Show Promising MRD Results and Safety in MDS/AML – Targeted Oncology | April 29th, 2022

Hairy cell leukemia is a rare type of blood cancer that can affect adults. In people who receive treatment, the long-term outlook for hairy cell leukemia is good.

Hairy cell leukemia (HCL) occurs when bone marrow produces too many white blood cells called lymphocytes.

The disease gets its name from the hairlike projections on its cells. HCL cells can affect the bone marrow, spleen, liver, and lymph nodes.

According to the National Organization for Rare Disorders, HCL is more common in males over the age of 50 years.

HCL affects roughly 6,000 people in the United States, with around 600800 new diagnoses each year. Around 12% of all adult leukemias are HCL.

In many cases, the long-term outlook for HCL is good, with people often continuing to live good-quality lives for years with medical care.

In this article, we look at the outlook and survival rates for HCL, the risk of secondary cancers, and treatment options.

Learn about the symptoms of HCL here.

HCL is a chronic disease, and although there is no cure for it, the condition is treatable. Treatment is usually highly effective and can help people continue to live normal lives.

According to the National Cancer Institute, HCL progresses slowly or does not worsen at all.

The Leukemia and Lymphoma Society reports that the 5-year event-free survival rate for HCL is 90% in people who received initial treatment with the chemotherapy drug cladribine. This means 90% of people will still be alive 5 years after diagnosis.

Treatment with cladribine has led to roughly 85% complete remission and around 10% partial response in people with HCL.

A 2020 study looked at survival rates in 279 people diagnosed with HCL between 1980 and 2011. The median age of the participants was 59 years old. In 208 of the participants, the first-line treatments were the drugs cladribine or pentostatin.

A 10-year follow-up found that the median survival rate was 27 years overall, with 11 years of relapse-free survival. There was a relapse rate of 39%. The study concluded that people with HCL have a good long-term outlook.

Research suggests that there may be racial disparities in HCL outcomes. A 2015 study included participants of the following racial groups:

The study found that the 10-year survival rate was worse in African American participants than in those of other racial groups.

Half of African American participants were alive at the 10-year follow-up, whereas more than two-thirds of those in other racial groups were alive at the follow-up.

The researchers concluded that the biological, socioeconomic, and health system factors contributing to this disparity need further investigation.

According to a 2020 study, people with HCL have an increased risk of secondary cancer.

Among 279 participants, 59 people developed at least one secondary cancer. The most common secondary cancers were prostate cancer, nonmelanoma skin cancer, and blood cancers.

The study did not find that treatment with purine analogs, such as cladribine or pentostatin, was a risk factor for secondary cancers.

However, according to the National Cancer Institute, cladribine and pentostatin may increase the risk of Hodgkin lymphoma and non-Hodgkin lymphoma.

Some research suggests that HCL and its effects on the body may increase the risk of secondary cancer.

People with HCL must attend regular cancer screenings to detect any early signs of secondary cancer.

Blood cell changes in those with HCL may result in compromised immune systems, making people more susceptible to infection or autoimmune disease.

HCL responds very well to treatment, which aims to manage the cancer rather than cure it.

Unlike with many other types of cancer, doctors may choose to wait before starting treatment.

Doctors will monitor the condition and may only begin treatment if they believe it is necessary to control it. This can help avoid any unnecessary side effects of treatment.

The type of treatment will depend on each condition but may include the following:

Cladribine and pentostatin are purine analogs, which are the first-line treatment for HCL.

According to the Hairy Cell Leukemia Foundation, both medications are highly effective treatments and can result in long-term remission.

In 2018, the Food and Drug Administration (FDA) approved another drug, moxetumomab pasudotox, to treat HCL. Doctors may use this drug in people who have not responded to standard therapies.

Interferon is a drug that doctors may use to treat HCL. Interferon uses the bodys immune system to help fight off cancer. Interferon affects how cancer cells divide and helps slow tumor growth.

Doctors may also use a biologic drug called rituximab, known by the brand name Rituxan, if people with HCL have not responded to other treatments. Rituximab is an antibody that attaches to HCL cells. Doctors may also use rituximab in combination with chemotherapy as a first-line treatment.

Targeted therapies use medications or other substances to find and destroy cancer cells. Targeted therapies may cause less harm to healthy cells than other treatments, such as radiation therapy or chemotherapy.

One type of targeted therapy to treat HCL is monoclonal antibody therapy. A laboratory creates antibodies that attach to cancer cells and destroy them or prevent them from growing and spreading. The biologic drug rituximab is an example of a monoclonal antibody.

Splenectomy is a surgical procedure to remove the spleen. This may be necessary if HCL causes an enlarged spleen.

However, doctors rarely perform splenectomy for HCL because there are medications that can effectively reduce the size of the spleen.

Learn more about immunotherapy for leukemia here.

Treatments for HCL can have the following side effects:

Cancer treatments may also cause other side effects, such as fatigue, appetite loss, or nausea.

Before starting treatment, people can discuss any potential side effects and the risks and benefits of each treatment option with their healthcare team.

Learn more about side effects here.

HCL is a rare type of leukemia. Other types of leukemia include:

HCL is a rare type of adult leukemia. It is more common in males over the age of 50 years.

The overall outlook for people with HCL is good. Treatment with chemotherapy drugs, such as cladribine and pentostatin, is highly effective and may result in long-term remission.

Treatments for HCL may have side effects. People can discuss any treatments potential risks and benefits with their healthcare team.

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Hairy cell leukemia: Outlook, treatment, and what to expect - Medical News Today

Bone Marrow Stem Cells Comments Off on Hairy cell leukemia: Outlook, treatment, and what to expect – Medical News Today | April 29th, 2022

Abstract: Glucose metabolism has been the focus of research in order to understand pathological conditions associated with diseases such as neonatal hypoxic-ischemic-encephalopathy (HIE), cerebral palsy (CP) and cerebral infarction.

Objective:To evaluate the use of molecular imaging (SPECT and PET) for children with HIE and CP before and after cell therapy, and to propose future perspectives on the use of those modalities for assessment of brain function in children with these conditions.

Methods:PubMed search for studies using PET or SPECT scans for HIE and CP in children.

Results:We identified 18 PET and 17 SPECT studies that have been performed in cases under age of 19 over the past three decades (19912021). Six papers on PET use consisted of one with human umbilical cord derived mesenchymal stromal cells, one mobilized peripheral blood mononuclear cells, three autologous bone marrow mononuclear cells and one allogeneic umbilical cord blood. 4/6 papers reported that PET-CT scan revealed increased glucose metabolism and 1/6 showed no significant change in glucose metabolism after cell therapy. One article on SPECT reported that 2/5 cases had improvement of cerebral perfusion in the thalamus after treatment.

Discussion:SPECT in the first few weeks of life is useful and more sensitive than MRI in predicting major neurological disability. SPECT is not appropriate for neonates because of the risk of radiation, improvement of other clinical test equipment. PET studies reported high glucose metabolism in the early neonatal periods in children with mild to moderate HIE, but not in the most severe cases, including those neonates that died.We suggested that PET could be more useful tool to estimate effectiveness of stem cell therapy than SPECT.

Conclusion:PET might be a good clinical modalities to clarify mechanism of stem cell therapy for CP. We need further clinical studies to clarify more precisely.

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Molecular Imaging (PET and SPECT) for Children with Hypoxic-ischemic-encephalopathy and Cerebral Palsy before and after cell therapy - Newswise

Bone Marrow Stem Cells Comments Off on Molecular Imaging (PET and SPECT) for Children with Hypoxic-ischemic-encephalopathy and Cerebral Palsy before and after cell therapy – Newswise | April 29th, 2022

Abstract

Arrhythmias are a major cardiac complication reported among patients with multiple myeloma (MM), but these have not been further characterized in this population. We explored the prevalence of arrhythmias and examined the predictors of mortality among patients with MM with arrhythmias. The National Inpatient Sample data collected between 2016 and 2018 were used to conduct retrospective analyses. Multivariable logistic regression analyses were done to examine the predictors of mortality among patients with MM with arrhythmias. 16.9% of patients with MM reported a diagnosis of any arrhythmias and 70.7% of these were atrial fibrillation. Patients aged 70 years and above had 21% lower odds (adjusted OR (AOR): 0.79; 95% CI: 0.68 to 0.92) of inpatient mortality relative to younger patients. Those in the non-Hispanic black, Hispanic, and non-Hispanic other category were 1.38 (95% CI: 1.16 to 1.64), 1.53 (95% CI: 1.19 to 1.97), and 1.69 (95% CI: 1.29 to 2.21) times more likely to die during hospitalization compared with their counterparts who were non-Hispanic whites. Relative to patients with MM who were on Medicare, those on private (AOR: 1.28; 95% CI: 1.06 to 1.54) and other insurance types (AOR: 1.78; 95% CI: 1.23 to 2.58) had higher odds of mortality. Other predictors of inpatient mortality were elective admission (AOR: 0.67; 95% CI: 0.52 to 0.85) and Charlson comorbidity indices between 57 (AOR: 1.23; 95% CI: 1.07 to 1.41) and 8 (AOR: 1.45; 95% CI: 1.21 to 1.73) compared with comorbidity indices between 0 and 4. Our study adds to the body of knowledge on the need for proper diagnosis and management of cardiac arrhythmias in patients with MM. Research is needed to further assess the time of arrhythmia diagnosis and its impact on health outcomes among patients with MM.

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Burden of arrhythmias and predictors of mortality among multiple myeloma patients with arrhythmias - Journal of Investigative Medicine

Bone Marrow Stem Cells Comments Off on Burden of arrhythmias and predictors of mortality among multiple myeloma patients with arrhythmias – Journal of Investigative Medicine | April 29th, 2022

Stem cell transplants can effectively cure a wide range of diseases, from blood cancers to rare genetic disorders. They've been used for decades and are considered standard treatment for certain conditions.

But for a good number of patients, stem cell transplants are out of reach. Drug regimens used to prepare the body for a transplant are toxic and can cause serious side effects. The transplanted cells don't always "engraft," or take root in the bone marrow. Even when they do, patients' disease may linger or recur.

A biotech startup launching Wednesday with $50 million in funding hopes that, by combining cell, antibody and gene editing technologies, at least some of these problems can be overcome. Called Cimeio Therapeutics, the new company is led by a team of pharmaceutical industry veterans and an advisory board filled with scientific luminaries, including immunologist Jeffrey Bluestone and gene editing pioneer Fyodor Urnov.

Cimeio's approach involves "shielding" transplanted cells by genetically editing them in ways that allows paired immunotherapies to be safely used both before and after a transplant.

Thomas Fuchs

Courtesy of Cimeio Therapeutics

"We think that this can really unleash the power of hematopoietic stem cell transplant and make a lot more patients eligible for it," said Thomas Fuchs, Cimeio's CEO and a former Genentech executive.

The "shielding" technology used by Cimeio was developed in Switzerland at the laboratory of Lukas Jeker, a physician-scientist from Basel University Hospital who will join Cimeio as head of gene editing.

Jeker's lab discovered that protein receptors on the surface of cells could be genetically edited in such a way that prevented antibodies from binding to them, while leaving their function intact. In preclinical testing, these edits could cloak, or "shield," the cells from being depleted by antibody drugs and T cell therapies.

The work could have powerful implications for improving stem cell transplant and adoptive cell therapy, according to Fuchs.

Once a stem cell or T cell is shielded, a complementary immunotherapy could be used to either help ready patients for a transplant or to further treat disease afterwards, he said. "Maybe you could give a cycle or two of the paired immunotherapy, implant the shielded cells and then continue to administer the immunotherapy," he added.

If the shielding works as intended, Cimeio could develop treatments for conditioning that are more tolerable than the chemotherapy or radiation-based regimens currently in use. Shielding might also allow existing drugs that target cell proteins on healthy as well as diseased cells to be used more flexibly with transplants, such as to treat residual disease that lingers afterwards.

For example, Cimeio could engineer stem cells that are protected against binding via a protein called CD19 that's often the target for CAR-T therapies that treat lymphoma, but is also found on healthy B cells that help the immune system fight off threats.

"One benefit could be that you could prevent a lifetime of B cell depletion, which happens when you give a CAR-T," said Fuchs.

Alex Mayweg

Courtesy of Cimeio Therapeutics

Cimeio was built from Jeker's lab by Versant Ventures at the company's "Ridgeline" incubator in Basel, which has previously produced companies like Monte Rosa Therapeutics and Black Diamond Therapeutics. The initial $50 million Versant provided will fund Cimeio through next year, said Alex Mayweg, a managing director at the venture firm and a Cimeio board member. Additional investors will be brought on later this year or early next, Mayweg said.

Cimeio will need the money, as its research and development plans are expansive. The company has identified four drug candidates already and envisions a dozen more behind those, said Fuchs. Its research spans blood cancers, rare genetic diseases and autoimmune disorders.

In some cases, Cimeio will develop paired immunotherapies to go with the shielded cells. In others, it will use existing treatments. Three of the first four candidates involve protecting hematopoietic stem cells, while the fourth involves T cells. The company hopes to begin human testing next year.

Cimeio plans to choose gene editing technologies based on the type of alteration it needs to make to shield cells. "Rather than building up an internal editing capability," Mayweg said, "we wanted to stay as flexible as possible."

That might mean partnerships or alliances with other companies, some of which have reached out to Cimeio already, according to Mayweg.

Cimeio is aided by a group of scientific advisers notable for their work in areas the company is focusing on. Urnov, of the University of California, Berkeley, is well known for his research in gene editing using zinc finger nucleases and CRISPR. Bluestone previously led the Parker Institute for Cancer Immunotherapy and is CEO of the cell therapy-focused biotech Sonoma Biotherapeutics.

Suneet Agarwal, a co-program leader of the stem cell transplant center at Boston Children's Cancer and Blood Disorders Center, is also on the advisory board, while Cimeio has a research collaboration in place with Matthew Porteus, a gene editing specialist at Stanford University.

About 20 people currently work at Cimeio directly, a number Fuchs expects will grow as the company's research advances. Another 15 are currently supporting Cimeio from Versant's Ridgeline group.

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Versant-backed startup launches with plans to broaden cell therapy's reach - BioPharma Dive

Bone Marrow Stem Cells Comments Off on Versant-backed startup launches with plans to broaden cell therapy’s reach – BioPharma Dive | April 15th, 2022

Investigators uncovered potential mechanisms of resistance to CD19-directed CAR T-cell therapy in patients with pediatric acute lymphoblastic leukemia.

Bone marrow samples from a trial examining CD19-directed CAR T-cell therapy helped investigators identify epigenetic biomarkers predicting resistance to therapy in pediatric acute lymphoblastic leukemia (ALL), according to a presentation from the 2022 American Association for Cancer Research (AACR) Annual Meeting.1

Investigators observed 3 key features of leukemia cells that do not respond to CAR T-cell therapy: hypermethylation of DNA, a stem cell-like phenotype and inherent plasticity, and decreased antigen presentation. These are independent of CD19 status and leukemia subtype, indicating a new predictive biomarker.

Whats most important about this is we can detect it prior to therapy in patient samples, so this highlights its potential as a biomarker for response, Katherine E. Masih, BS, an NIH-Cambridge scholar in the Genetics Branch, Center for Cancer Research at the National Cancer Institute, said in a press conference. We hope that eventually this can improve patient selection and eligibility for CD19 CAR T-cell therapy.

CD19 is a common target of CAR T cells, and resistance to treatment can occur even if patients continue to show CD19 expression. The investigators explored primary non-response (PNR) to CAR T-cell therapy, which occurs in 10% to 20% of patients and whose causes are not fully understood. Known reasons for non-response to CAR T cells include collection of dysfunctional T cells and decreased death cell receptors on the cell surface.2,3

The investigators used bone marrow samples from 14 participants in the PLAT-02 trial (NCT02028455) of CD19-directed CAR T-cell therapy for relapsed/refractory pediatric ALL.1 These samples included those of 7 patients who had a complete response to therapy and 7 who had no response. Non-response was defined as not achieving and maintaining minimal residual disease negativity at 63 days.

A multiomic analysis of the bone marrow included whole-exome sequencing, RNA sequencing of the bulk cells, single-cell RNA sequencing, array-based methylation analysis, and ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing).

In patients who went on to have PNR, investigators discovered epigenetic markers including 238 regions of hypermethylated DNA, which is associated with inactivated genes (P = 8.15 10-25). These regions are known to be activated in stem cells.

The ATAC-seq analysis showed increased accessibility of chromatin at regions linked to stem cell proliferation (normalized enrichment score [NES] = 2.31; P < .0001) and cell cycling (NES = 2.27; P < .0001), indicating inherent plasticity that may allow leukemia cells to adapt to resist CAR T-cell therapy.

Investigators found that the epigenetic differences did not lead to differences in phenotype of B cells between primary sensitive and PNR patients. However, PNR cells did show an increase in regions associated with hematopoietic stem cells and myeloid and lymphoid progenitors. In addition, investigators observed decreased antigen presentation and processing that could lead to lack of response in cells that still express CD19 (P = .0001).

These factors characterized a potential novel biomarker associated with PNR that investigators named Stem-Cell Epigenome with Multi-Lineage Potential (SCE-MLP). Masih acknowledged that the sample size of 14 patients was small and more research on SCE-MLPs link to PNR is needed. We would love to see this validated in a larger cohort with more cases of PNR that exist around the country, she said.

Another potential use of SCE-MLP could be to find ways to overcome resistance to CAR T-cell therapy by combining it with targeted therapies that disrupt these epigenetic factors for resistance.

Currently, the investigators hope that this research will be used to shape patient selection for CAR T-cell therapy and alternative therapies.

If we can reliably identify responders, perhaps through screening for SCE-MLP, we can prioritize less toxic targeted therapies for our patients and overall improve outcomes for children with this devastating disease, Masih said.

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Molecular Characteristics of Resistance to CD19-Directed CAR T Cells Revealed in Pediatric ALL - Cancer Network

Bone Marrow Stem Cells Comments Off on Molecular Characteristics of Resistance to CD19-Directed CAR T Cells Revealed in Pediatric ALL – Cancer Network | April 15th, 2022