AS one of the most common childhood cancers around, chances are you know what leukaemia is.

But can you actually name any of the symptoms associated with the deadly illness?

1

According to results of a recent survey, less than1 per cent of Britsare able to identify all four common symptoms of the cancer.

Leukaemia is a type of blood cancer that affects people of all ages, with 10,000 people getting diagnosed in the UK every year.

Overall survival rate for the disease stands at just over 50 per cent, making it one of the most deadly forms of cancer.

However, a survey conducted by two cancer charities found that over two-fifths (42 per cent) of people cannot recognise any of the four most widely reported symptoms of the disease.

It also revealed that 43 per cent people wrongly think leukaemia is most common in the under 24s.

Common leukaemia signs and symptoms include:

Leukaemia a type of blood cancer that affects cells in bone marrow and attacks the immune system.

The most common symptoms are:

Other symptoms of leukaemia include:

Fiona Hazell, chief executive ofLeukaemia UK-- one of the charities who published the survey-- believe this mistaken belief could cost lives.

"In reality, both incidence and mortality rates rise sharply after the age of 55," she explained.

"Raising awareness in this age group is critical in order to treat it early and effectively; and ultimately to improve survival rates overall," she said.

Like with all cancers, catching leukaemia early means treatment is more likely to be successful.

In response to the survey results, Leukaemia UKand Leukaemia Care have together launched a new campaign -- called #SpotLeukaemia -- to make people more aware of the symptoms.

Zack Pemberton-Whiteley, chief executive ofLeukaemia Care also said the results of the survey were "extremely worrying."

"It's crucial that if you think you have fatigue, bruising or bleeding or repeated infections that you contact your GP and ask for a blood test. It's as simple as that," he said.

There are four main types of leukaemia.

They are:

Acute Lymphocytic Leukaemia (ALL)-A rapidly progressing form of the disease.More common in children.

Acute Myeloid Leukaemia (AML) -Rapidly progressive. More common in adults.

Chronic Lymphocytic Leukaemia (CLL) -Slowly progressing form and more common in adults.

Chronic Myeloid Leukaemia (CML) -Progresses slowly and is more common in adults.

Cancer types, signs and symptoms

Everything you need to know about different types of Cancer

Currently there are five ways leukaemia can be treated.

They are:

Chemotherapy-These are cell-killing drugs which kill and/or stop them from dividing. Chemotherapy is often given in blocks or cycles of treatment.One cycle of treatment will consist of a series of doses of chemotherapy followed by a break for the healthy cells to recover.

Radiation therapy -This treatment uses high-energy radiation to kill cancer cells. It is not used to treat all types of leukaemia.

Targeted therapy -Drugs which specifically recognise and kill leukaemia cells.

Biological therapy -A treatment which uses the immune system to destroy leukaemia cells.

Stem cell transplant -Youngerpatients may be given a stem cell transplant (bone marrow transplant). This may be done using your own healthy stem cells or stem cells from a donor. This is most commonly done for acute leukaemia if chemotherapy does not cure the disease.

Read more:
Urgent warning as millions of Brits dont know the key signs of deadly cancer... - The US Sun

Bone Marrow Stem Cells Comments Off on Urgent warning as millions of Brits dont know the key signs of deadly cancer… – The US Sun | August 26th, 2022

A type of blood cell cancer called angioimmunoblastic T-cell lymphoma (AITL) can develop as mutations accumulate with age in the stem cells from which the T cells in the blood develop.

However, the underlying mechanism by which AITL develops was unknown. Now, a team from the University of Tsukuba in Japan have shown that B cells, another type of blood cells, accumulate mutations in genes that control how the genetic material in the cell is packaged. These aberrant B cells then interact with T cells and lead to the development of AITL.

The paper, Clonal germinal center B cells function as a niche for T-cell lymphoma, was published in the journal Blood.

Blood cells such as B cells and T cells, involved in immunity, develop from stem cells in the bone marrow. Sometimes, mutations occur in individual stem cells that lead to the mutant stem cell giving an increased output of blood cells, all of which carry identical mutations.

The likelihood of this increases with age, known as age-related clonal hematopoiesis, or ACH. ACH is known to be linked to various cancers. AITL, a cancer of the T cells, is linked to ACH with mutations in a gene called TET2. The team used mouse models and human samples to show that theTET2 mutation needed to be present in all blood cells, not just the T cells, for a mouse model to develop AITL.

Using single-cell RNA sequencing, a technique that can show which genes are active within just one cell, they were able to profile the immune cells present in the samples. This revealed a significant increase in the number of aberrant germinal center B cells, a type of B cells with activating and proliferative capacities. These B cells showed recurrent mutations to genes for histone proteins, which organize the genetic material in the cell into higher structures. They also showed alterations to the pattern of a DNA modification called methylation, which affects the genes expressed in the cell.

B cells and T cells can interact through molecules on the cell surface known as CD40 and CD40 ligand.

Analysis of the single-cell sequencing data identified this interaction between CD40 and CD40 ligand as potentially essential for mediating crosstalk between the aberrant B cells and the tumor cells, said lead author Manabu Fujisawa.

Most importantly, the survival of the mice with AITL could be prolonged by treatment with an antibody designed to inhibit CD40 ligand, said main author Mamiko Sakata-Yanagimoto.

The genes expressed in the aberrant mouse GCB cells are also expressed in cells from human AITL withTET2 mutations.

This means that antibodies against CD40 ligand could potentially be a new therapeutic approach to human AITL.

The rest is here:
University of Tsukuba researchers understand the mechanism of AITL - Labiotech.eu

Bone Marrow Stem Cells Comments Off on University of Tsukuba researchers understand the mechanism of AITL – Labiotech.eu | August 26th, 2022

Certain patients with Wilm's tumor-expressing solid tumors are eligible to be treated with an investigational agent in a phase 1 clinical trial.

The first patient was dosed in a phase 1 dose escalation study (NCT05360680) which is evaluating CUE-102, of the interleukin 2 (IL-2) series, as monotherapy for the treatment of patients with Wilms Tumor 1 (WT1)-positive recurrent/metastatic cancers. The study will focus on colorectal, gastric, pancreatic, and ovarian cancers, according to a press release from Cue Biopharma.1

CUE-102 has the potential to activate the patients immune system against numerous WT1-expressing cancers, including solid tumors and hematologic malignancies, and has demonstrated selective and significant activation of WT1-specific T cells in preclinical studies. We believe that CUE-102 can play an important role in changing the treatment landscape for patients with WT1-positive cancers, by potentially delivering higher efficacy and lower toxicities than current available treatments, said Ken Pienta, MD, acting chief medical officer of Cue Biopharma, in a press release.

In a preclinical study of CUE-102 tested humans with peripheral blood mononuclear cells (PBMC) for cellular activity and specificity, while in vivo CUE-102 is testing in mice who are human leukocyte antigen HLA-A2 transgenic. Investigators found that CUE-102 both activates and expands WT1-specific CD8-positive T cells from PBMC of healthy donors. Similar to results seen with CUE-101, CUE-102 showed significant functional reduction of the IL-2 components.The in vivo study found CUE-102 expands polyfunctional WT1-specific CD8-positive T cells from mice who were nave and previously immunized, but the treatment did not alter the frequencies of other immune lineages.The in vivo study also found the WT1-specific CD8-positive T cells had a polyfunctional response to peptide-loaded target cells and selectively killed WT1-presenting target cells.These results, along with a tolerable safety profile, support the initiation of the phase 1 trial of CUE-102.2

This phase 1 study aims to find the dose-limiting toxicity and maximum-tolerated dose of CUE-102. The secondary end points include safety and tolerability, antitumor response rate, antitumor duration of response, antitumor clinical benefit rate, progression-free survival, and overall survival. The dose escalation portion of the trial will administer CUE-102 in intravenous doses of 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, and an experimental recommended phase 2 dose every 3 weeks for up to 2 years.3

Eligible patients in this phase 1 study will include patients who have colorectal, gastric, pancreatic, or ovarian cancer who have an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, have a human leukocyte antigen (HLA)-A*0201 genotype as determined by genomic testing, and tumors who are WT1-positive. Patients will be deemed ineligible if patients with central nervous system metastases have been treated and be asymptomatic, have a history of prior allogeneic bone marrow, stem cell, or solid organ transplant, treatment with radiation therapy within 14 days before the first dose of CUE-102, and a history of clinically significant cardiovascular disease.3

Initiating this phase 1 clinical study of CUE-102 at a starting dose of 1mg/kg, a clinically active dose in our Phase 1 CUE-101 clinical trial for HPV+ head and neck cancer, is an important step forward in demonstrating the modularity of our Immuno-STAT platform and the broader clinical potential of our CUE-100 series of biologics, said Dan Passeri, chief executive officer of Cue Biopharma, in the press release. We believe, given the preservation of the core molecular framework between CUE-102 and CUE-101 with the primary exception of the tumor-specific epitope, initiating the dose escalation trial at 1 mg/kg will result in reduced time and cost to evaluate tolerability at therapeutically active doses.

References

1. Cue biopharma doses first patient in phase 1 study of CUE-102 for Wilms Tumor 1 (WT1) - expressing cancers. Press release. Cue Biopharma; August 22, 2022. Accessed August 23, 2022. https://www.cuebiopharma.com/investors-media/news/

2. Zhang C, Girgis N, Merazga Z, et al. 720CUE-102 selectively activates and expands WT1-specific T cells for the treatment of patients with WT1+ malignancies. Journal for ImmunoTherapy of Cancer. 2021;9:doi: 10.1136/jitc-2021-SITC2021.720

3. A phase 1 in patients with HLA-A*0201+ and WT1+ recurrent/metastatic cancers. ClinicalTrials.gov. Updated July 7, 2022. Accessed August 23, 2022. https://clinicaltrials.gov/ct2/show/record/NCT05360680?term=NCT05360680&draw=2&rank=1&view=recor

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Phase 1 Trial of CUE-102 in WT1+ Solid Tumors is Now in Motion - Targeted Oncology

Bone Marrow Stem Cells Comments Off on Phase 1 Trial of CUE-102 in WT1+ Solid Tumors is Now in Motion – Targeted Oncology | August 26th, 2022

MIAMI, Aug. 25, 2022 (GLOBE NEWSWIRE) -- LongeveronInc. (NASDAQ: LGVN),a clinical stage biotechnology company developing cellular therapies for chronic, aging-related and life-threatening conditions, today announced that the European Patent Office (EPO) has issued a notice of its intent to grant the Company a patent (EP Application No. 15861319.0) related to methods to treat endothelial dysfunction and monitor the efficacy of allogeneic mesenchymal cell therapies, also known as medicinal signaling cells (MSCs). The cells are administered to patients with cardiovascular disease through the monitoring of a protein, Vascular Endothelial Growth Factor (VEGF), which is a signal protein produced by many cells that stimulates the formation of blood vessels.

We are extremely pleased to receive this notice from the European patent office, said Chris Min, M.D., Ph.D., Interim Chief Executive Officer and Chief Medical Officer at Longeveron. This patent will bolster our robust intellectual property portfolio and support our goal of delivering effective cell therapies for a range of aging-related and life-threatening conditions.

The patent is titled Methods for Monitoring Efficacy of Allogeneic Mesenchymal Stem Cell Therapy in a Subject. Longeverons lead investigational product is Lomecel-B, a cell therapy product derived from MSCs. Many of Longeverons clinical studies point to Lomecel-B exerting effects through pro-vascular functions and/or reducing endothelial dysfunction, a condition where the lining of blood vessels is abnormal leading to diminished health of blood vessels and blood flow regulation.

The Company is evaluating the use of MSCs to treat several indications, including Hypoplastic Left Heart Syndrome (HLHS), a rare and life-threatening congenital heart defect that affects approximately 1,000 babies per year. Longeveron received both a Rare Pediatric Disease Designation and Orphan Drug Designation from the United States Food and Drug Administration in 2021 for Lomecel-B for the treatment of infants with HLHS. Longeveron is currently evaluating Lomecel-B for HLHS in a Phase 2a trial.

Longeveron is also conducting a trial of Lomecel-B in patients with Alzheimers Disease in the US and for aging frailty in Japan.

Now that the European Patent Office has issued an Intention to Grant, Longeveron will await grant of the patent and then begin the process of registering the patent in a number of nation members of the European Patent Organization. In those jurisdictions where the patent is registered, the patent is expected to expire in November of 2035.

About Longeveron Inc.

Longeveron is a clinical stage biotechnology company developing cellular therapies for specific aging-related and life-threatening conditions. The Companys lead investigational product is the Lomecel-B cell-based therapy product, which is derived from culture-expanded medicinal signaling cells (MSCs) that are sourced from bone marrow of young, healthy adult donors. Longeveron believes that by using the same cells that promote tissue repair, organ maintenance, and immune system function, it can develop safe and effective therapies for some of the most difficult disorders associated with the aging process and other medical disorders. Longeveron is currently sponsoring Phase 1 and 2 clinical trials in the following indications: Alzheimers disease, hypoplastic left heart syndrome (HLHS), Aging Frailty, and Acute Respiratory Distress Syndrome (ARDS). Additional information about the Company is available at http://www.longeveron.com.

Cautionary Note Regarding Forward-Looking Statements

Certain statements in this press release that are not historical facts are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, which reflect management's current expectations, assumptions, and estimates of future performance and economic conditions, and involve risks and uncertainties that could cause actual results to differ materially from those anticipated by the statements made herein. Forward-looking statements are generally identifiable by the use of forward-looking terminology such as "believe," "expects," "may," "looks to," "will," "should," "plan," "intend," "on condition," "target," "see," "potential," "estimates," "preliminary," or "anticipates" or the negative thereof or comparable terminology, or by discussion of strategy or goals or other future events, circumstances, or effects. Factors that could cause actual results to differ materially from those expressed or implied in any forward-looking statements in this release include, but are not limited to, statements about the ability of Longeverons clinical trials to demonstrate safety and efficacy of the Companys product candidates, and other positive results; the timing and focus of the Companys ongoing and future preclinical studies and clinical trials and the reporting of data from those studies and trials; the size of the market opportunity for the Companys product candidates, including its estimates of the number of patients who suffer from the diseases being targeted; the success of competing therapies that are or may become available; the beneficial characteristics, safety, efficacy and therapeutic effects of the Companys product candidates; the Companys ability to obtain and maintain regulatory approval of its product candidates; the Companys plans relating to the further development of its product candidates, including additional disease states or indications it may pursue; existing regulations and regulatory developments in the U.S., Japan and other jurisdictions; the Companys plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available and its ability to avoid infringing the intellectual property rights of others; the need to hire additional personnel and the Companys ability to attract and retain such personnel; the Companys estimates regarding expenses, future revenue, capital requirements and needs for additional financing; the Companys need to raise additional capital, and the difficulties it may face in obtaining access to capital, and the dilutive impact it may have on its investors; the Companys financial performance, and the period over which it estimates its existing cash and cash equivalents will be sufficient to fund its future operating expenses and capital expenditures requirements. Further information relating to factors that may impact the Company's results and forward-looking statements are disclosed in the Company's filings with the Securities and Exchange Commission, including Longeverons Annual Report on Form 10-K for the year ended December 31, 2021, filed with the SEC on March 11, 2022, and the Companys Quarterly Reports on Form 10-Q for the periods ended March 31, 2022, and June 30, 2022. The forward-looking statements contained in this press release are made as of the date of this press release, and the Company disclaims any intention or obligation, other than imposed by law, to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

Investor Contact:

Elsie YauStern IR, Inc.212-698-8700elsie.yau@sternir.com

More:
Longeveron Receives Intent to Grant Notice from the European Patent Office for Methods to Monitor Efficacy of Lomecel-B - BioSpace

Bone Marrow Stem Cells Comments Off on Longeveron Receives Intent to Grant Notice from the European Patent Office for Methods to Monitor Efficacy of Lomecel-B – BioSpace | August 26th, 2022

New York, Aug. 23, 2022 (GLOBE NEWSWIRE) -- Kenneth Research has published a detailed market report on Global Cell Banking Outsourcing Market for the forecast period, i.e., 2022 2031, which includes the following factors:

Global Cell Banking Outsourcing Market Size:

The global cell banking outsourcing market generated the revenue of approximately USD 7200.1 million in the year 2021 and is expected to garner a significant revenue by the end of 2031, growing at a CAGR of ~18% over the forecast period, i.e., 2022 2031. The growth of the market can primarily be attributed to the development of advanced preservation techniques for cells, and increasing adoption of regenerative cell therapies for the treatment of chronic diseases such as cancer. Additionally, factors such as growing demand for gene therapy, and increasing worldwide prevalence of cancer are expected to drive the market growth. According to the World Health Organization, nearly 10 million people died of cancer across the globe in 2020. The most recurrent cases of deaths because of cancer were lung cancer which caused 1.80 million deaths, colon, and rectum cancer which caused 916 000 deaths, liver cancer which caused 830 000 deaths, stomach cancer which caused 769 000 deaths, and breast cancer which caused 685 000 deaths. Furthermore, it was noticed that about 30% of cancer cases in low and lower-middle income nations are caused by cancer-causing diseases such the human papillomavirus (HPV) and hepatitis.

Get a Sample PDF of This Report @ https://www.kennethresearch.com/sample-request-10070777

Global Cell Banking Outsourcing Market: Key Takeaways

Increasing Geriatric Population across the Globe to Boost Market Growth

Increasing demand for stem cell therapy, and increasing biopharmaceutical production are estimated to fuel the growth of the global cell banking outsourcing market. Among the geriatric population around the world, the demand of stem cell therapy is at quite a high rate. Hence, growing geriatric population across the globe is also expected be an important factor to influence the market growth. According to the data by World Health Organisation (WHO), the number and proportion of geriatric population, meaning the people aged 60 years and older in the population is rising. The number of people aged 60 years and older was 1 billion in 2019. This number is estimated to increase to 1.4 billion by 2030 and 2.1 billion by 2050.

In addition to this, increasing prevalence of chronic diseases, supportive initiatives by governments around the world, and growing awareness about stem cell banking are predicted to be major factors to propel the growth of the market. The growth of the global cell banking outsourcing market, over the forecast period, can be further ascribed to the rising investments in the R&D activities to continuously bring up more feasible solutions for medical procedures. According to research reports, since 2000, global research and development expenditure has more than tripled in real terms, rising from approximately USD 680 billion to over USD 2.5 trillion in 2019.

Browse to access In-depth research report on Global Cell Banking Outsourcing Market with detailed charts and figures: https://www.kennethresearch.com/report-details/cell-banking-outsourcing-market/10070777

Global Cell Banking Outsourcing Market: Regional Overview

The global cell banking outsourcing market is segmented into five major regions including North America, Europe, Asia Pacific, Latin America, and the Middle East and Africa region.

Advanced Healthcare Facilities Drove Market in the North America Region

The market in the North America region held the largest market share in terms of revenue in the year 2021. The growth of the market in this region is majorly associated with the increasing number of pharmaceutical companies & manufacturers in the region, and increasing awareness for the use of stem cells as therapeutics. Increasing number of bone marrow and cord blood transplants throughout the region is also estimated to positively influence the market growth. It was noted that, 4,864 unrelated and 4,160 related bone marrow and cord blood transplants were performed in the United States in 2020.

Increasing Prevalence of Chronic Diseases to Influence Market Growth in the Asia Pacific Region

On the other hand, market in the Asia Pacific region is estimated to grow with the highest CAGR during the forecast period. The market in this region is driven by the increasing investment in biotechnology sector by government and private companies specifically in countries such as China, India, and Japan. Moreover, the increasing pool of patient with chronic diseases, such as cancer, and the ongoing research & development activities for cancer treatment is expected to propel the growth of the market. Further, increasing percentage of regional health expenditure contributing to the GDP is also estimated to be a significant factor to influence the growth of the cell banking outsourcing market in the Asia Pacific region. As per The World Bank, in the year 2019, share of global health expenditure in East Asia & Pacific region accounted to 6.67% of GDP.

Get a Sample PDF of the Global Cell Banking Outsourcing Market @ https://www.kennethresearch.com/sample-request-10070777

The study further incorporates Y-O-Y growth, demand & supply and forecast future opportunity in:

Middle East and Africa (Israel, GCC [Saudi Arabia, UAE, Bahrain, Kuwait, Qatar, Oman], North Africa, South Africa, Rest of Middle East and Africa).

Global Cell Banking Outsourcing Market, Segmentation by Bank Phase

The bank storage segment held the largest market share in the year 2021 and is expected to maintain its share by growing with a notable CAGR during the forecast period. The market growth is anticipated to be driven by the development of effective preservation technologies such as cryopreservation technique. Cryopreservation is a technique in which low temperature is used to preserve the living cells and tissue for a longer time. With the growing healthcare expenditure per capita across the world, demand for bank storage increasing notably. As sourced from The World Bank, in 2019, worldwide health expenditure per capita was USD 1121.97.

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Global Cell Banking Outsourcing Market, Segmentation by Product

The adult cell banking segment is estimated to hold a substantial market share in the global cell banking outsourcing market during the forecast period. The growth of this segment can be attributed to the significant prevalence of chronic diseases among the adults around the globe. For instance, according to the National Library of Medicine 71.8% of adult population suffered from cardiovascular diseases, 56% had diabetes, and 14.7% adults had arthritis as of 2020.

Global Cell Banking Outsourcing Market, Segmentation by Cell Type

Global Cell Banking Outsourcing Market, Segmentation by Bank Type

Few of the well-known market leaders in the global cell banking outsourcing market that are profiled by Kenneth Research are SGS SA, WuXi AppTec, LifeCell International Pvt. Ltd., BSL Bioservice, LUMITOS AG, Cryo-Cell International, Inc., REPROCELL Inc, CORDLIFE GROUP LIMITED, Reliance Life Sciences, and Clean Biologics and others.Enquiry before Buying This Report @ https://www.kennethresearch.com/sample-request-10070777

Recent Developments in the Global Cell Banking Outsourcing Market

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About Kenneth Research

Kenneth Research is a leading service provider for strategic market research and consulting. We aim to provide unbiased, unparalleled market insights and industry analysis to help industries, conglomerates and executives to take wise decisions for their future marketing strategy, expansion and investment, etc. We believe every business can expand to its new horizon, provided a right guidance at a right time is available through strategic minds. Our out of box thinking helps our clients to take wise decision so as to avoid future uncertainties.

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Global Cell Banking Outsourcing Market to Grow at a CAGR of ~18% during 2022-2031; Market to Expand Owing to the Development of Advanced Cell...

Bone Marrow Stem Cells Comments Off on Global Cell Banking Outsourcing Market to Grow at a CAGR of ~18% during 2022-2031; Market to Expand Owing to the Development of Advanced Cell… | August 26th, 2022

MONDAY, Aug. 22, 2022 (HealthDay News) -- The COVID-19 pandemic was associated with a decrease in transplantation in 2020, according to a study published in the July 1 issue of the American Journal of Surgery.

Alejandro Suarez-Pierre, M.D., from the University of Colorado School of Medicine in Aurora, and colleagues examined adult transplantation data as time series data in a population-based cohort study. Models of transplantation rates were developed using data from 1990 to 2019 to project the expected 2020 rates in a theoretical scenario in which the pandemic did not occur. Observed-to-expected (O/E) ratios were calculated for transplants.

The researchers found that 32,594 transplants were expected in 2020, but 30,566 occurred (O/E, 0.94; 95 percent confidence interval, 0.88 to 0.99). A total of 50,241 waitlist registrations occurred compared with 58,152 expected (O/E, 0.86; 95 percent confidence interval, 0.80 to 0.94). For kidney, liver, heart, and lung, the O/E ratios (95 percent confidence intervals) of transplants were 0.92 (0.86 to 0.98), 0.96 (0.89 to 1.04), 1.05 (0.91 to 1.23), and 0.92 (0.82 to 1.04), respectively. The corresponding O/E ratios (95 percent confidence intervals) of waitlist registrations were 0.84 (0.77 to 0.93), 0.95 (0.86 to 1.06), 0.99 (0.85 to 1.18), and 0.80 (0.70 to 0.94).

"The COVID-19 pandemic was associated with a significant deficit in solid organ transplantation, donation, and waitlist registrations in the United States in 2020. The impact was strongest in kidney transplantation and waitlist registration," the authors write. "While the pandemic persisted through 2020, the transplant system adapted remarkably well with a record number of transplantations performed."

Abstract/Full Text

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Drop Seen in Transplantation in 2020 With COVID-19 Pandemic - Consumer Health News | HealthDay - HealthDay News

Bone Marrow Stem Cells Comments Off on Drop Seen in Transplantation in 2020 With COVID-19 Pandemic – Consumer Health News | HealthDay – HealthDay News | August 26th, 2022

SOMERVILLE, Mass.--(BUSINESS WIRE)--Cellarity, a life sciences company founded by Flagship Pioneering to transform the way medicines are created, announced today the release of a unique single-cell dataset to accelerate innovation in mapping multimodal genetic information across cell states and over time. This dataset will be used to power a competition hosted by Open Problems in Single-Cell Analysis.

Cells are among the most complex and dynamic systems and are regulated by the interplay of DNA, RNA, and proteins. Recent technological advances have made it possible to measure these cellular features and such data provide, for the first time, a direct and comprehensive view spanning the layers of gene regulation that drive biological systems and give rise to disease.

Advancements in single-cell technologies now make it possible to decode genetic regulation, and we are excited to generate another first-of-its-kind dataset to support Open Problems in Single Cell Analysis, said Fabrice Chouraqui, PharmD, CEO of Cellarity and a CEO-Partner at Flagship Pioneering. Developing new machine learning algorithms that can predict how a single-cell genome can drive a diversity of cellular states will provide new insights into how cells and tissues move from health to disease and support informed design of new medicines.

To drive innovation for such data, Cellarity generated a time course profiling in vitro differentiation of blood progenitors, a dataset designed in collaboration with scientists at Yale University, Chan Zuckerberg Biohub, and Helmholtz Munich. This time course will be used to power a competition to develop algorithms that learn the underlying relationships between DNA, RNA, and protein modalities across time. Solving this open problem will help elucidate complex regulatory processes that are the foundation for cell differentiation in health and disease.

While multimodal single-cell data is increasingly available, methods to analyze these data are still scarce and often treat cells as static snapshots without modeling the underlying dynamics of cell state, said Daniel Burkhardt, Ph.D., cofounder of Open Problems in Single-Cell Analysis and Machine Learning Scientist at Cellarity. New machine learning algorithms are needed to learn the rules that govern complex cell regulatory processes so we can predict how cell state changes over time. We hope these new algorithms can augment the value of existing or future single-modality datasets, which can be cost effectively generated at higher quality to streamline and accelerate research.

In 2021, Cellarity partnered with Open Problems collaborators to develop the first benchmark competition for multimodal single-cell data integration using a first-of-its-kind multi-omics benchmarking dataset (NeurIPS 2021). This dataset was the largest atlas of the human bone marrow measured across DNA, RNA, and proteins and was used to predict one modality from another and learn representations of multiple modalities measured in the same cells. The 2021 competition saw winning submissions from both computational biologists with deep single-cell expertise and machine learning practitioners for whom this competition marked their first foray into biology. This translation of knowledge across disciplines is expected to drive more powerful algorithms to learn fundamental rules of biology.

For 2022, Cellarity and Open Problems are extending the challenge to drive innovation in modeling temporal single-cell data measured in multiple modalities at multiple time points. For this years competition, Cellarity generated a 300,000-cell time course dataset of CD34+ hematopoietic stem and progenitor cells (HSPC) from four human donors at five time points. HSPCs are stem cells that give rise to all other cells in the blood throughout adult life, and a 10-day time course captures important biology in CD34+ HSPCs. Being able to solve the prediction problems over time is expected to yield new insights into how gene regulation influences differentiation.

Entries to the competition will be accepted until November 15, 2022. For more information, visit the competition page on Kaggle.

About Open Problems in Single Cell Analysis

Open Problems in Single-Cell Analysis was founded in 2020 bringing together academic, non-profit, and for-profit institutions to accelerate innovation in single-cell algorithm development. An explosion in single-cell analysis algorithms has resulted in more than 1,200 methods published in the last five years. However, few standard benchmarks exist for single-cell biology, both making it difficult to identify top performing algorithms and hindering collaboration with the machine learning community to accelerate single-cell science. Open Problems is a first-of-its-kind international consortium developing a centralized, open-source, and continuously updated framework for benchmarking single-cell algorithms to drive innovation and alignment in the field. For more information, visit https://openproblems.bio/.

About Cellarity

Cellaritys mission is to fundamentally transform the way medicines are created. Founded by Flagship Pioneering in 2017, Cellarity has developed unique capabilities combining high-resolution data, single cell technologies, and machine learning to encode biology, predict interventions, and purposefully design breakthrough medicines. By focusing on the cellular changes that underlie disease instead of a single target, Cellaritys approach uncovers new biology and treatments and is applicable to a vast array of disease areas. The company currently has programs underway in metabolic disease, hematology, immuno-oncology, and respiratory disease. For more info, visit http://www.cellarity.com.

About Flagship Pioneering

Flagship Pioneering conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. Since its launch in 2000, the firm has, through its Flagship Labs unit, applied its unique hypothesis-driven innovation process to originate and foster more than 100 scientific ventures, resulting in more than $100 billion in aggregate value. To date, Flagship has deployed over $2.9 billion in capital toward the founding and growth of its pioneering companies alongside more than $19 billion of follow-on investments from other institutions. The current Flagship ecosystem comprises 41 transformative companies, including Denali Therapeutics (NASDAQ: DNLI), Evelo Biosciences (NASDAQ: EVLO), Foghorn Therapeutics (NASDAQ: FHTX), Moderna (NASDAQ: MRNA), Omega Therapeutics (NASDAQ: OMGA), Rubius Therapeutics (NASDAQ: RUBY), Sana Biotechnology (NASDAQ: SANA), and Seres Therapeutics (NASDAQ: MCRB).

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Cellarity Releases Novel, Open-Source, Single-Cell Dataset and Invites the Machine Learning and Computational Biology Communities to Develop New...

Bone Marrow Stem Cells Comments Off on Cellarity Releases Novel, Open-Source, Single-Cell Dataset and Invites the Machine Learning and Computational Biology Communities to Develop New… | August 18th, 2022

My gold standard would be the use of an orthobiologic joint treatment, such as autologous protein solution, as it would be the least invasive joint treatment for a pregnant mare as only one injection is recommended, while other regenerative products often recommend a series of treatments for best effects, she adds.

Orthobiologic treatments are processed using the horses own blood, often stallside, to isolate properties beneficial to the joint. These treatments can provide targeted pain relief without the potential negative physiological and metabolic side effects (e.g., spontaneous abortion, harm to the fetus) of steroid use. The downside is these treatments are significantly more expensive than steroids.

In most cases I would feel comfortable injecting a fetlock joint in a pregnant mare with a low dose of a steroid such as triamcinolone if I felt it was indicated for the quality of life of the mare and orthobiologic treatments were not an option financially, Crosby says. Treatment with polyacrylamide (hydro)gel (PAAG) could also be considered, although (manufacturers of) these formulations often recommend pretreatment with a steroid for best effects. Polyacrylamide gel works by reducing friction in a joint, which can be a very effective option for advanced arthritis.

Fitz is a 14-year-old Morgan gelding with early onset pituitary pars intermedia dysfunction (PPID, formerly equine Cushings disease). His condition is well-controlled on 1 milligram of pergolide (Prascend) daily, and his owner shows him regularly in saddle seat shows. Earlier this year Fitz was diagnosed with coffin joint osteoarthritis. He improved on a polysulfated glycosaminoglycan (Adequan) series but is still experiencing performance issues.

Bonny Henderson, DVM, IVCA, CVA, CREP, owner of Henderson Equine Clinic, in Avon, New York, is a huge proponent of adjunct therapies. Prior to injections she recommends her clients try a variety of nutraceuticals to provide building blocks for the healing process and to decrease systemic inflammation. She says shes had incredible results with this approach.

I like to combine Eastern and Western medicine for my patients, Henderson says. I try to get people to treat the whole horse, identify what is causing the lameness and why exactly the cause occurredin other words, the functional limitations predisposing the horse to the injury itself. Then I treat both the lameness and the underlying cause.

This case requires careful attention because of the horses endocrine disease. PPID horses can be more sensitive to steroids, and this can result in laminitis, says Henderson. Even if hes well-maintained, you have to take into account his body condition score and hoof capsule. If the hoof capsule contains external growth rings wider in the heel than the toe, youve likely had some prior clinical or subclinical (not showing obvious signs) laminitic episodes. There is a lot of concussion going through these horses feet; ground force reactions are much more pronounced due to the shoeing package and actions of the horse and have a greater impact on the hoof. You have to watch out for a subclinical condition of what we used to term road founder that would compound the metabolic issue of PPID.

In these complex cases Henderson says she reaches for an orthobiologic. I would first ultrasound this joint to visualize the health of the cartilage, she says. If there is cartilage present, I would start with an autologous protein solution. If the lameness is from an injury or if there is a lot of (inflammation in the joint fluid), I would recommend injecting -2 macroglobulin, followed by the autologous protein solution once the inflammation is resolved.

The -2 macroglobulin injections are relatively novel treatments in equine practice. This orthobiologic isolates the horses natural -2 macroglobulin, a potent anti-inflammatory with molecules typically too large to cross into the joint. The veterinarian can then inject the -2 macroglobulin into the joint to reduce the synovitis (joint inflammation) without the negative effects of corticosteroids.

Clover is a 22-year-old Thoroughbred mare. She is a retired racehorse-turned-jumper-turned-dressage horse. Her multitude of careers has left her with relatively severe carpal arthritis of her right forelimb, with osteochondral fragments and excessive bony changes. She has a very caring owner who has tried just about anything to keep the mare comfortable, including rounds of polysulfated glycosaminoglycan, intravenous hyaluronic acid, and systemic anti-inflammatories. Clover is still lame and resistant to flexion of the carpus. This joint is end-stage.

When osteophytes (bone spurs) are present in a joint, they are not usually the direct cause of a horses pain. In my experience, the greater pain comes from synovitis and the lack of cartilage. I would talk to the owner about -2 macroglobulin, because these cases often require a multiple-layered treatment plan, says Henderson. I would also recommend following the -2 macroglobulin with a 2.5% polyacrylamide hydrogel once the severe inflammation is controlled.

Researchers have shown that the 2.5% PAAG provides the synovial lining with structure and stability and facilitates increased production of joint fluid. The integration of the product into the membrane, thickening the structure, also provides shock absorption. It essentially increases joint lubrication and provides a cushion in these end-stage joints.

Often, horses with end-stage OA stop responding to medical management, at which point surgical fusion of the joint can offer long-term comfort.

Cole is an 8-year-old Warmblood stallion who competes in the hunter/jumper ring. His attending veterinarian has diagnosed him via radiographs and computed tomography with osteoarthritic changes in his distal cervical vertebrae, causing a left forelimb lameness.

Cervical pain and dysfunction in the horse has become increasingly recognized as a cause of poor performance and can be more involved than just pain originating from the joint proper, says Michael Caruso III, VMD, Dipl. ACVS-LA, owner of Reedsdale Equine Specialists, in Nashville, Tennessee, who specializes in equine lameness diagnosis and treatment.

While OA can affect any joint, the cervical vertebrae can be an insidious location. Osteoarthritis of the cervical articular process joints (is) obviously a disease of the cartilage surface and bone, but other structures are involved and intimately associated with the joint, including the joint capsule, synovium, subchondral bone (beneath the cartilage), and paraspinal muscles, Caruso explains.

Because cervical OA is so complex, vets must combine multiple methods to treat it. I believe that many horses with cervical facet joint pain/osteoarthritis require a multimodal approach to treatment depending upon the age of the horse and severity of the dysfunction, he says. We know that horses with neck arthritis can present with a wide range of issues, from poor performance and intermittent forelimb lameness to ataxia (incoordination).

Cervical joint OA can disrupt the adjacent spinal cord nerve roots, causing this neurologic manifestation.

Injection must be performed using ultrasound guidance, Caruso says. I would inject the articular process joints with a corticosteroid (betamethasone or triamcinolone), plus or minus hyaluronic acid, plus or minus (the antimicrobial) amikacin and, depending on the horses range of motion and muscle tension, might prescribe a muscle relaxant (methocarbamol) and/or perform mesotherapy and shock wave for any muscular/fascial pain adjacent to the affected joints.

Caruso says he would take any metabolic issues into account before injecting corticosteroids. In horses that have some sort of metabolic dysfunction, I will routinely utilize orthobiologics in the affected joints, he says, adding that his personal preferences are platelet-rich plasma (PRP) and autologous conditioned serum.

All horses treated for cervical pain are prescribed therapeutic rehabilitation, Caruso says. Dynamic exercises of not only the cervical region but also the whole body appear to positively affect muscle activation and strengthening. The exercise program aims to improve joint stability and range of motion by focusing on the deep paravertebral muscles.

Remington is a 6-year-old Warmblood gelding who competes in the jumpers. He becomes lame in the right hind, and his veterinarian isolates the lameness to the stifle. On imaging, the medial (toward the midline) meniscus looks enlarged and mottled. He is referred for an arthroscopy of his medial femorotibial joint. The surgeon suggests injecting it six weeks following the procedure.

With this case, Caruso says hed first recommend injecting mesenchymal stem cells (MSCs) into the medial femorotibial joint. While we have lots to learn about stem cells, in the stifleespecially postoperatively with meniscal damagestem cells have been shown to improve the long-term outcome for return to work in the horse, he says.

He cites one study (Ferris et al., 2014) on the outcome of horses undergoing stifle surgery plus bone-marrow-derived mesenchymal stem cell injections. The researchers found that of the horses treated for stifle injury with surgery and stem cells, 75% returned to some level of work postoperatively, which compares to previous reports of 60-63% with surgery alone.

The stifle is one joint that I will recommend injection with bone-marrow-derived MSCs following arthroscopic surgery as a first-line treatment, Caruso says. This is one joint that I believe stem cells have an advantage if finances allow.

Veterinarians typically harvest stem cells from the horse at the time of surgery, usually from the sternum, pelvis, or tibia. While they have potent healing factors, they are generally more expensive than the other orthobiologics mentioned. If an owner cant afford that price tag following stifle surgery, Caruso recommends PRP.

Clinically, I see a great response (from PRP) both in soft tissues and in joints, he says. I feel that MSC injection in stifle cases with proper rehabilitation following meniscal injury are more successful with less convalescent time.

While joint injection techniques are well-documented, the tricky part is what goes into the syringe. Gone are the days of simple corticosteroid injections as our only optionthough theyre still used and have a place in equine medicine. The insights from these veterinarians show we have several ways to approach a lameness, especially a complicated joint case.

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Equine Joint Injections: Case by Case The Horse - TheHorse.com

Bone Marrow Stem Cells Comments Off on Equine Joint Injections: Case by Case The Horse – TheHorse.com | August 18th, 2022

A bone marrow transplant is a medical procedure that replacesthe bone marrow with healthy cells. Replacement cells might come from either ones own body or from a donor. A stem cell transplant, or more specifically, a hematopoietic stem cell transplant, is another name for a bone marrow transplant. Transplantation can be used to treat leukemia, myeloma, and lymphoma, as well as other blood and immune system illnesses that impact the bone marrow. Cancer and cancer treatment can damage the hematopoietic stem cells. Hematopoietic stem cells are blood-forming stem cells. Hematopoietic stem cells that are damaged may not develop into red blood cells, white blood cells, or platelets. These blood cells are vital, and each one serves a specific purpose. A bone marrow transplant can help the body regenerate the red blood cells, white blood cells, and platelets it requires.

The global Bone Marrow Transplant market is estimated to be valued at $10,356.1 Mn Mn in 2021 and is expected to exhibit a CAGR of 4.0% over the forecast period (2022-2028).

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The study provides data on the most exact revenue estimates for the complete market and its segments to aid industry leaders and new participants in this market. The purpose of this study is to help stakeholders better understand the competitive landscape and design suitable go-to-market strategies. The market size, features, and growth of theBone Marrow Transplantindustry are segmented by type, application, and consumption area in this study. Furthermore, key sections of the GlobalBone Marrow Transplantmarket are evaluated based on their performance, such as cost of production, dispatch, application, volume of usage, and arrangement.

Competitive Analysis: Global Bone Marrow Transplant Market

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: United States, Canada, and Mexico & : Argentina, Chile, Brazil and Others & : Saudi Arabia, UAE, Israel, Turkey, Egypt, South Africa & Rest of MEA. : UK, France, Italy, Germany, Spain, BeNeLux, Russia, NORDIC Nations and Rest of Europe. -: India, China, Japan, South Korea, Indonesia, Thailand, Singapore, Australia and Rest of APAC.

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Company profiles, revenue sharing, and SWOT analyses of the major players in theBone Marrow TransplantMarket are also included in the research. TheBone Marrow Transplantindustry research offers a thorough examination of the key aspects that are changing, allowing you to stay ahead of the competition. These market measuring methods assist in the identification of market drivers, constraints, weaknesses, opportunities, and threats in the global market.

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Increasing efforts to set up centers for Bone Marrow Transplant is expected to Boost the growth of the market, Top Key players | Lonza, Merck KgaA,...

Bone Marrow Stem Cells Comments Off on Increasing efforts to set up centers for Bone Marrow Transplant is expected to Boost the growth of the market, Top Key players | Lonza, Merck KgaA,… | August 10th, 2022

Tracing features in a large 3D electron microscopy dataset reveals a zebrafish blood stem cell (in green) and its surrounding niche support cells, a group photo method that will help researchers understand factors that contribute to blood stem cell health which could in turn help develop therapies for blood diseases and cancers. Image by Keunyoung Kim.

MADISON For the first time, researchers can get a high-resolution view of single blood stem cells thanks to a little help from microscopy and zebrafish.

Researchers at the University of WisconsinMadison and the University of California San Diego have developed a method for scientists to track a single blood stem cell in a live organism and then describe the ultrastructure, or architecture, of that same cell using electron microscopy. This new technique will aid researchers as they develop therapies for blood diseases and cancers.

Currently, we look at stem cells in tissues with a limited number of markers and at low resolution, but we are missing so much information, says Owen Tamplin, an assistant professor in UWMadisons Department of Cell & Regenerative Biology, a member of the Stem Cell & Regenerative Medicine Center, and a co-author on the new study, which was published Aug. 9 in eLife. Using our new techniques, we can now see not only the stem cell, but also all the surrounding niche cells that are in contact.

The niche is a microenvironment found within tissues like the bone marrow that contain the blood stem cells that support the blood system. The niche is where specialized interactions between blood stem cells and their neighboring cells occur every second, but these interactions are hard to track and not clearly understood.

As a part of the new study, Tamplin and his co-lead author, Mark Ellisman, a professor of neuroscience at UC San Diego, identified a way to integrate multiple types of microscopic imaging to investigate a cells niche. With the newly developed technique that uses confocal microscopy, X-ray microscopy, and serial block-face scanningelectron microscopy, researchers will now be able to track the once elusive cell-cell interactions occurring in this space.

This has allowed us to identify cell types in the microenvironment that we didnt even know interacted with stem cells, which is opening new research directions, Tamplin says.

As a part of this study, Tamplin, and his colleagues, including co-first authors Sobhika Agarwala and Keunyoung Kim, identified dopamine beta-hydroxylase positive ganglia cells, which were previously an uncharacterized cell type in the blood stem cell niche. This is crucial, as understanding the role of neurotransmitters like dopamine in regulating blood stem cells could lead to improved therapeutics.

Transplanted blood stem cells are used as a curative therapy for many blood diseases and cancers, but blood stem cells are very rare and difficult to locate in a living organism, Tamplin says. That makes it very challenging to characterize them and understand how they interact and connect with neighboring cells.

While blood stem cells are difficult to locate in most living organisms, the zebrafish larva, which is transparent, offers researchers a unique opportunity to view the inner workings of the blood stem cell niche more easily.

Thats the really nice thing about the zebrafish and being able to image the cells, Tamplin says of animals transparent quality. In mammals, blood stem cells develop in utero in the bone marrow, which makes it basically impossible to see those events happening in real time. But, with zebrafish you can actually watch the stem cell arrive through circulation, find the niche, attach to it, and then go in and lodge there.

While the zebrafish larva makes it easier to see blood stem cell development, specialized imaging is needed to find such small cells and then detail their ultrastructure. Tamplin and his colleagues spent over six years perfecting these imaging techniques. This allowed them to see and track the real-time development of a blood stem cell in the microenvironment of a live organism, then zoom in even further on the same cell using electron microscopy.

First, we identified single fluorescently labeledstem cells bylight sheet or confocal microscopy, Tamplin says. Next, we processed the same sample forserial block-face scanningelectron microscopy. We then aligned the 3D light and electron microscopy datasets. Byintersecting these different imaging techniques,we could see the ultrastructure of single rare cells deep inside a tissue. This also allowed us to find all the surrounding niche cellsthat contact a blood stem cell. We believe our approach will be broadly applicable for correlative light and electron microscopy in many systems.

Tamplin hopes that this approach can be used for many other types of stem cells, such as those in the gut, lung, and the tumor microenvironment, where rare cells need to be characterized at nanometer resolution. But, as a developmental biologist, Tamplin is especially excited to see how this work can improve researchers understanding of how the blood stem cell microenvironment forms.

I think this is really exciting because we generate all of our blood stem cells during embryonic development, and depending on what organism you are, a few hundred or maybe a few thousand of these stem cells will end up producing hundreds of billions of new blood cells every day throughout your life, Tamplin says. But we really dont know much about how stem cells first find their home in the niche where theyre going to be for the rest of the life of the organism. This research will really help us to understand how stem cells behave and function. A better understanding of stem cell behavior, and regulation by surrounding niche cells, could lead to improved stem cell-based therapies.

This research was supported by grants from the National Institutes of Health (R01HL142998, K01DK103908, 1U24NS120055-01, R24 GM137200) and the American Heart Association (19POST34380221).

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See-through zebrafish, new imaging method put blood stem cells in high-resolution spotlight - University of Wisconsin-Madison

Bone Marrow Stem Cells Comments Off on See-through zebrafish, new imaging method put blood stem cells in high-resolution spotlight – University of Wisconsin-Madison | August 10th, 2022

Cell membrane-coated nanoparticles, applied in targeted drug delivery strategies, combine the intrinsic advantages of synthetic nanoparticles and cell membranes. Although stem cell-based delivery systems were highlighted for their targeting capability in tumor therapy, inappropriate stem cells may promote tumor growth.

Study:Stem cell membrane-camouflaged targeted delivery system in tumor. Image Credit:pinkeyes/Shutterstock.com

A review published in the journalMaterials Today Biosummarized the role of stem cell membrane-camouflaged targeted delivery system in tumor therapy and focused on the underlying mechanisms of stem cell homing toward target tumors. Nanoparticle-coated stem cell membranes have enhanced targetability, biocompatibility, and drug loading capacity.

Furthermore, the clinical applications of induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) were investigated as membrane-camouflaged targeted delivery systems for their anti-tumor therapies. In concurrence, the stem cell membrane-coated nanoparticles have immense prospects in tumor therapy.

Cell-based targeted delivery systems have low immunogenicity and toxicity, innate targeting capability, ability to integrate receptors, and long circulation time. Cells such as red blood cells, platelets, stem cells, tumor cells, immune cells, and even viral/bacterial cells can serve as effective natural vesicles.

MSCs derived from the umbilical cord (UC-MSCs), bone marrow (BM-MSCs), and adipose tissue (ATMSCs) are utilized in clinical applications. However, iPSCs are preferable over MSCs in clinical applications due to their easy fetch by transcription factor-based reprogramming of differentiation of somatic cells.

Stem cells (MSCs/ iPSCs) can be easily isolated and used as drug delivery systems for tumor therapy. Stem cell-based delivery systems have inflammation or tumor lesions targeting capacity. However, stem cells are often entrapped in the lung due to their size, resulting in microembolism.

Cell membrane-coated nanoparticles are applied in targeted delivery strategies. To this end, stem cell membrane-coated nanoparticles have tremendous prospects in biomedical applications. Although previous reports mentioned the role of cell membrane-coated nanocarriers in tumor therapy, delivery systems based on stem cell membranes have not been explored extensively.

Stem cell membrane-coated nanoparticles obtained from stem cells have complex functioning and can achieve biological interfacing. Consequently, stem cell membrane-coated nanoparticles served as novel drug delivery systems that could effectively target the tumor.

Previous reports mentioned the preparation of doxorubicin (DOX) loaded, poly (lactic-co-glycolic acid) (PLGA) coated MSC membrane-based nanovesicles, which showed higher cellular uptake than their PLGA uncoated counterparts. Similarly, the DOX-loaded MSC membrane-coated gelatin nanogels showed enhanced storage stability and sustained drug release.

Thus, the stem cell membrane-coated nanoparticles served as novel carriers for stem cells and facilitated the targeted delivery of the drugs at the tumor site. Since the stem cell membrane-coated nanoparticles had good targeting and penetration abilities, they enhanced the efficiency of chemotherapeutic agents in tumor therapy and minimized the side effects.

Reactive oxygen species (ROS) based photodynamic therapy (PDT) is mediated by photosensitizers with laser irradiations. Previous reports mentioned the development of MSC membrane-based mesoporous silica up-conversion ([emailprotected]2) nanoparticles that efficiently targeted the tumor due to their high affinity after being coated with MSC membrane.

These cell membrane-coated nanoparticles showed high cytocompatibility (with hepatocyte cells) and hemocompatibility (with blood). Moreover, the [emailprotected]2 nanoparticles-based PDT therapy under 980-nanometer laser irradiations could inhibit the tumors in vivo and in vitro. Consequently, the stem cell membrane-coated nanoparticles had circulation for an extended time and escaped the immune system, thereby increasing their accumulation at the tumor site.

Stem cell membrane-coated nanoparticles were also applied to deliver small interfering RNA (siRNA) via magnetic hyperthermia therapy and imaging. Previous reports mentioned the preparation of superparamagnetic iron oxide (SPIO) nanoparticles using an MSC membrane that reduced the immune response.

Additionally, the CD44 adhesion receptors were preserved on the surface of the MSC membrane during preparation. These prepared nanovesicles were unrecognized by macrophages, which enabled their stability in blood circulation. The nanosize and tumor homing capacity of MSCs helped the nanovesicles generate a dark contrast in T2-weight magnetic resonance imaging (MRI).

Cell membrane-coated nanoparticles helped fabricate various targeted delivery strategies. Especially, stem cell membrane-coated nanoparticles have the following advantages: stem cells are easy to isolate and expand in vitro. Thus, multilineage potential and phenotypes could be preserved for more than 50 population doublings in vitro.

Stem cell membrane-coated nanoparticles also have an intrinsic capacity to target inflammation or tumor lesions. Hence, these nanoparticles were established for tumor therapy, building a strong foundation for stem cell membrane-mediated delivery systems.

On the other hand, stem cell membrane-coated nanoparticles have the following drawbacks: Despite various sources for collecting MSCs (UC-MSCs/BM-MSCs/ATMSCs), the number of cells obtained is limited, although iPSCs are relatively easy to fetch by reprogramming differentiated somatic cells, the reprogramming is a high-cost step, restricting the clinical applications of iPSCs.

Zhang, W., Huang, X. (2022). Stem cell membrane-camouflaged targeted delivery system in tumor. Materials Today Bio.https://www.sciencedirect.com/science/article/pii/S2590006422001752

Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.

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Stem Cell Membrane-Coated Nanoparticles in Tumor Therapy - AZoNano

Bone Marrow Stem Cells Comments Off on Stem Cell Membrane-Coated Nanoparticles in Tumor Therapy – AZoNano | August 10th, 2022

TCR-CAR+ iPSC-derived CD8 T Cells Induced Complete and Durable Responses In Vivo in Systemic Leukemia Model

Cell-surface Markers, Gene Transcription Profile, and In Vivo Anti-tumor Activity of TCR-CAR+ iPSC-derived CD8 T Cells Compared Favorably with Healthy-donor Peripheral Blood CAR T Cells

Phase 1 Study Ongoing of First-ever iPSC-derived T-cell Product Candidate FT819 for Off-the-shelf Treatment of Patients with Relapsed / Refractory B-cell Malignancies

SAN DIEGO, Aug. 09, 2022 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. ( FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, today announced the publication of preclinical study results demonstrating the successful generation, durable anti-tumor response, and functional persistence of TCR-CAR+ iPSC-derived CD8 T cells from induced pluripotent stem cells (iPSCs). The CD8 T cells were derived from a single engineered iPSC integrating a novel chimeric antigen receptor (CAR) transgene into the T-cell receptor alpha constant (TRAC) locus, ensuring complete bi-allelic disruption of T-cell receptor (TCR) expression and promoting uniform CAR expression. The discoveries were made under a multi-year research collaboration between the Company and Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, and were published this week in Nature Biomedical Engineering.

Scientists have previously differentiated induced pluripotent stem cells to form CAR T cells, however, it was observed that premature TCR or constitutive CAR expression resulted in the derivation of innate-like T cells that do not acquire the phenotype nor exhibit the function of conventional CD8 T cells, said Dr. Sadelain. Our published findings are the first to show the generation of iPSC-derived CD8 CAR T cells lacking a TCR, where timed and calibrated expression of the CAR in place of the TCR successfully drove T-cell maturation and promoted the acquisition of a transcriptional and functional profile more closely resembling that of natural CD8 T cells.

The mass production of TCR-CAR+ CD8 T cells from master engineered iPSC lines is a promising approach for development of off-the-shelf, cell-based cancer immunotherapies. Through a systematic assessment of factors that affect T-cell lineage commitment and induce adaptive T-cell formation, the researchers discovered that integrating the CAR construct into the TRAC locus delayed its expression and drove T-cell lineage commitment, and that regulation of CAR signaling strength promoted the generation of CD4+CD8+ double-positive cells mimicking thymic development in the absence of a TCR. Subsequent stimulation of the CAR matured the double-positive population into single-positive CD8 T cells with a phenotype highly correlated with peripheral blood CD8 effector T cells and distinct from T cells and natural killer cells. Preclinical studies showed that iPSC-derived TCR-CAR+ CD8 T cells were able to repeatedly lyse tumor cells in vitro and durably control leukemia in vivo, with persistence in the bone marrow, spleen, and blood, in a systemic NALM6 leukemia model.

These published findings continue to support our unique ability to generate TCR-CAR+ CD8 T cells from master engineered iPSC lines that exhibit a phenotypic profile and anti-tumor activity comparable to healthy donor-derived peripheral blood CAR T cells in preclinical model systems, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. We believe our off-the-shelf, iPSC-derived CAR T cell programs overcome the numerous challenges associated with the manufacture, consistency, and reach of autologous and allogeneic CAR T cells, and we look forward to sharing initial clinical data from our landmark Phase 1 study of FT819 later this year.

The Company is conducting a multicenter Phase 1 study of FT819, the first T-cell therapy manufactured from a clonal master iPSC line to undergo clinical investigation. The product candidates clonal engineered master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct integrated into the TRAC locus, ensuring complete bi-allelic disruption of TCR expression to prevent graft-versus-host disease and promoting uniform CAR expression for enhanced anti-tumor activity. Dose escalation is currently ongoing in single-dose and multi-dose escalation cohorts for relapsed / refractory B-cell malignancies.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics has licensed intellectual property from MSK on which Dr. Sadelain is an inventor. As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the Companys progress, plans and timelines for the manufacture and clinical investigation of its product candidates, the Companys initiation and continuation of enrollment in its clinical trials including additional dose cohorts in ongoing clinical trials of its product candidates, the therapeutic and market potential of the Companys product candidates, and the Companys clinical development strategy, including for its product candidate FT819. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Companys product candidates may not demonstrate the requisite safety or efficacy to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Companys product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Companys product candidates or in the initiation and conduct of, or enrollment of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Companys product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Companys ongoing and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of FT819 may not be replicated in ongoing or future clinical trials, and the risk that FT819 may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200[emailprotected]

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Fate Therapeutics Announces Preclinical Publication Highlighting Derivation of CD8 T Cells from TCR-CAR+ Induced Pluripotent Stem Cells -...

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HAEMOGLOBIN IS a protein in your red blood cells. Your red blood cells carry oxygen throughout your body. If you have a condition that affects your bodys ability to make red blood cells, your haemoglobin levels may drop. Low haemoglobin levels may be a symptom of several conditions, including different kinds of anaemia and cancer.

If a disease or condition affects your bodys ability to produce red blood cells, your haemoglobin levels may drop. When your haemoglobin level is low, it means your body is not getting enough oxygen, making you feel very tired and weak.

Normal haemoglobin levels are different for men and women. For men, a normal level ranges between 14.0 grams per decilitre (gm/dL) and 17.5 gm/dL. For women, a normal level ranges between 12.3 gm/dL and 15.3 gm/dL. A severe low-haemoglobin level for men is 13.5 gm/dL or lower. For women, a severe low haemoglobin level is 12 gm/dL.

Your doctor diagnoses low haemoglobin by taking samples of your blood and measuring the amount of haemoglobin in it. This is a haemoglobin test. They may also analyse different types of haemoglobin in your red blood cells, or haemoglobin electrophoresis.

Several factors affect haemoglobin levels and the following situations may be among them:

Your body produces red blood cells and white blood cells in your bone marrow. Sometimes, conditions and diseases affect your bone marrows ability to produce or support enough red blood cells.

Your body produces enough red blood cells, but the cells are dying faster than your body can replace them.

You are losing blood from injury or illness. You lose iron any time you lose blood. Sometimes, women have low haemoglobin levels when they have their periods. You may also lose blood if you have internal bleeding, such as a bleeding ulcer.

Your body cannot absorb iron, which affects your bodys ability to develop red blood cells.

You are not getting enough essential nutrients like iron and vitamins B12 and B9.

Your bone marrow produces red blood cells. Diseases, conditions and other factors that affect red blood cell production include:

Lymphoma: This is a term for cancers in your lymphatic system. If you have lymphoma cells in your bone marrow, those cells can crowd out red blood cells, reducing the number of red blood cells.

Leukaemia: This is cancer of your blood and bone marrow. Leukaemia cells in your bone marrow can limit the number of red blood cells your bone marrow produces.

Anaemia: There are many kinds of anaemias involving low-haemoglobin levels. For example, if you have aplastic anaemia, the stem cells in your bone marrow dont create enough blood cells. In pernicious anaemia, an autoimmune disorder keeps your body from absorbing vitamin B12. Without enough B12, your body produces fewer red blood cells.

Multiple Myeloma: This causes your body to develop abnormal plasma cells that may displace red blood cells.

Chronic Kidney Disease: Your kidneys dont produce the hormone that signals to your bone marrow to make red blood cells. Chronic kidney disease affects this process.

Antiretroviral medications: These medications treat certain viruses. Sometimes these medications damage your bone marrow, affecting its ability to make enough red blood cells.

Chemotherapy: Chemotherapy may affect bone marrow cells, reducing the number of red blood cells your bone marrow produces.

Doctors treat low haemoglobin by diagnosing the underlying cause. For example, if your haemoglobin levels are low, your healthcare provider may do tests that reveal you have iron-deficiency anaemia. If that is your situation, they will treat your anaemia with supplements. They may recommend that you try to follow an iron-rich diet. In most cases, treating the underlying cause of anaemia will bring the haemoglobin level up.

Many things can cause low haemoglobin, and most of the time you cannot manage low haemoglobin on your own. But eating a vitamin-rich diet can help maintain your red blood cells. Generally, a balanced diet with a focus on important nutrients is the best way to maintain healthy red blood cells and haemoglobin.

keisha.hill@gleanerjm.comSOURCE: Centres for Disease Control and Prevention

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Factors that affect haemoglobin levels and how to detect when it's low - Jamaica Gleaner

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The media continues the one-handed count of patients that seem to be cured of HIV as a man who has lived with the disease since the 1980s has been in remission for 17 months.

The story is always the samethey seem to be cured, and they get a cool nicknamein this case the City of Hope Patient, after Duarte, California, where he was treated.

The difference in this case was the treatmenta bone marrow transplant to treat blood cancer leukemia from a donor who was naturally resistant to the virus.

The most remarkable difference however, is that he is only patient cured of HIV by coincidence.

The man had developed leukemia, and took the bone marrow transplant for that reason. As it happened, the donor was resistant to HIV, and taught the mans body to create an immune response against the virus.

RELATED: Worlds Second Person Cured of HIV: 40-Year-old Man is Confirmed to Be 30 Months Virus-Free

This is also the first one who got it during the epidemic of HIV/AIDS that took so many lives.

When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence, said the City of Hope Patient. I never thought I would live to see the day that I no longer have HIV.

SIMILAR: Two Patients Make History After Essentially Being Cured of HIV Using Stem Cell Transplant

So far, only three people have been seemingly cured of human immunodeficiency virus (HIV) which weakens the bodys immune system and leads to the more severe AIDS (autoimmune deficiency syndrome) which can be lethal.

The man no longer takes antiretroviral drugs, the only treatment for HIV. A bone marrow transplant is not a likely future cure, do to it being a tricky and side-effectual procedure.

Nevertheless, all cure cases have been those where a patient is given a transplant of some kind, mostly stem cells, that contain the very rarely occurring natural immunity to the virus.

The case was reported at the AIDS 2022 conference in Montreal, Canada.

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Fourth Patient Seemingly Cured of HIV Through Wild Coincidence - Good News Network

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IrelandUruguay, Eastern Republic ofUzbekistanVanuatuVenezuela, Bolivarian Republic ofViet Nam, Socialist Republic ofWallis and Futuna IslandsWestern SaharaYemenZambia, Republic ofZimbabwe

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BUDDY SCOTT: Love stems from the Father | Brazos Living | thefacts.com - Brazosport Facts

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MANY people suffer with back pain, whether that's from poor posture or a sporting injury.

Teenager Daniel Greer had been struggling with this - as well as neck pain.

2

2

But rather than an injury or pull - a blood test confirmed a shocking diagnosis.

The 14-year-old from Northern Ireland was told he had acute myeloid leukaemia two months ago.

Now his family are racing to find a stem cell donor - as this is his only chance of survival.

Since his diagnosis, the music fanatic has been staying at the Royal Belfast Hospital for Sick Children and is being treated with aggressive chemotherapy.

Doctors say that a stem cell transplant will help repair his immune system - but only one in four people will find a match within their own family.

His older brother James, sadly isn't a match so Daniel will need a transplant from an unrelated donor.

Mum, Anne, is now speaking out in the hopes of getting more people to sign up to the stem cell register - with the possibility of finding her son a donor.

She said: "Daniel is an amazing, bright young man who lights up any room he walks into.

"His wicked sense of humour keeps our spirits up, even now while hes in hospital receiving chemotherapy.

"I know hes really proud that his story is inspiring people to sign up to the stem cell register.

"Those people will potentially help him, as well as many other people around the world who desperately need a stem cell transplant like Daniel."

When it comes to the stem cell register, young men make up just 18 per cent of those on it, blood cancer charity Anthony Nolan states.

However, this demographic also makes up more than half of all stem cell transplants for blood cancer and blood disorder patients.

Now the charity is helping with an international appeal to get Daniel a donor, dubbed the DoItForDaniel campaign.

Daniel, lives in Newry and so far local pharmacies have got behind the campaign - urging people to sign up to help save the lives of others.

What is leukaemia?

Leukaemia is a type of blood cancer that affects cells in bone marrow and attacks the immune system.

In most cases of leukaemia, there is no obvious cause. Little Azaylia had been diagnosed with Acute Myeloid Leukaemia (AML) , which is a rapidly progressive form of the illness.

Leukaemia is a cancer that leads to the body making too many abnormal white blood cells and means the body is less likely to be able to defend itself against infection.

These blood cells are not fully developed and are called leukaemia cells.

The disease is often classified as the type of cell affected (myeloid or lymphatic) and how it progresses (acute or chronic).

There are four main types of leukaemia.

Acute Lymphocytic Leukaemia (ALL)-A rapidly progressing form of the disease.More common in children.

Acute Myeloid Leukaemia (AML) -Rapidly progressive. More common in adults.

Chronic Lymphocytic Leukaemia (CLL) -Slowly progressing form and more common in adults.

Chronic Myeloid Leukaemia (CML) -Progresses slowly and is more common in adults

There has also been an awareness-raising drive about stem cell donation at Belfast International Airport.

It's hoped that the drive will allow the keen mountain biker and rugby player to continue to do the things he enjoys most.

Anthony Nolan chief executive Henny Braund said that finding a matching donor would mean everything to Daniel and his family.

"We are committed to supporting Daniel as he waits for news of the donor who could save his life.

Last year over 1,300 people around the world with blood cancer or a blood disorder were given a second chance of life because of the wonderful people that are signed up to the Anthony Nolan register.

But too many people, like Daniel, are told there is no matching donor for them.

Signing up to the register is quick and simple, and we urge anyone who is in good general health, especially young men aged 16-30, to come forward and potentially save the life of someone like Daniel.

Anyone aged 16-30 can sign up online through the Anthony Nolan website.

DONATING STEM CELLS & SIGNING THE REGISTER

When you join a stem cell registry you are on standby to be matched and potentially save a life although many people are never called up.

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My little boy is fighting for his life after complaining of back pain you could save him... - The Sun

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Type 1 diabetes (T1D) is a chronic immune-mediated disease characterized by the destruction of pancreatic -cells, resulting in absolute insulin deficiency and hyperglycemia. It is primarily a disease of youth, accounting for approximately 85% of cases in people under the age of 20 and 5% to 10% of all diagnosed cases of diabetes [1,2]. Although the exact mechanisms are unknown, T1D is thought to develop through immune system activation against -cell antigens and the initiation of proinflammatory cytokine responses. Environmental factors, obesity, viral infections, and nutritional factors were found to play a role in the pathophysiology as well [3]. T1D predisposes to a number of comorbidities, such as obesity, chronic kidney disease, metabolic syndrome, coronary artery disease, and hypertension. Such predispositions may account for higher mortality rates, affecting up to one in 10 adult patients within a year of diagnosis [4]. In fact, diabetic nephropathy (DN) is said to account for up to 40% of end-stage renal disease (ESRD) cases worldwide. Cardiovascular events account for up to 70% of T1D deaths and are 10 times more common in diabetics than in non-diabetics [5]. Therefore, it is critical to focus on novel therapies that aim to reduce the risks of acute complications such as hypoglycemia and diabetic ketoacidosis (DKA) while avoiding long-term complications such as DN, neuropathy, and retinopathy [5].

Exogenous insulin is currently the most prevalent treatment for T1D. Although exogenous insulin administration may be life-saving, it is not a cure for the disease. If patients are unable to maintain tight glycemic control by strictly adhering to their insulin regimen, they will invariably develop severe secondary complications that may shorten their life span [6]. Exogenous insulin is not a viable substitute for normal pancreatic islet function, mainly due to the absence of accurate temporal glucose control over time [7]. The administration of insulin can also result in hypoglycemic episodes [6]. A cross-sectional study conducted in Mexico revealed that patients' fear of hypoglycemic episodes prevented them from complying with their insulin treatment plan [8].

Replacement of the defective insulin-producing cells (IPC) is yet another potential therapy for T1D. This is possible through transplantation of the pancreas. Since the first pancreatic transplant took place in 1966, over 50,000 such transplants have been performed worldwide. Patients with T1D who receive a pancreatic transplant were found to have a reduced risk of subsequent complications and a longer life expectancy [9]. However, since transplantation is a major surgical procedure, patients must be fit for surgery [6]. Transplants necessitate permanent immunosuppression, which may put patients at risk for a variety of infections. In addition, they are associated with a number of postoperative complications, such as pancreatitis, due to low tolerance to cold ischemia, bleeding, thrombosis, and anastomotic leakage, which may require relaparotomy and graft pancreatectomy in recipients [9].

An alternative to pancreatic transplantation that is both safe and effective is islet cell transplantation. Scharp et al. published the first case of allogeneic intraportal islet transplantation for T1D in 1990, which led to short-term insulin independence and paved the way for clinical islet transplantation [10]. Despite the fact that the immunosuppressive regimen reported from Edmonton, Canada, also known as the Edmonton protocol (the Edmonton protocol introduced significant adjustments to the transplantation procedure, including the use of an immunosuppressive regimen free of steroids and the transplanting of an average islet mass of 11,000 islet equivalents per kilogram) has achieved unprecedented success in islet transplantation in terms of insulin independence, a number of factors continue to influence the outcome of this minimally invasive procedure [11]. Islet cell transplantation can induce a rapid inflammatory reaction in the circulation, leading to the loss of the vast majority of transplanted islets. The use of large doses of immunosuppressants during transplantation compromises the long-term viability and function of the graft, and the need for long-term immunosuppressive medications after the transplant poses a risk of organ damage, malignancies, new infections, and new-onset T1D in patients [12]. The high cost of islet transplantation and the paucity of human cadaveric islets highlight the urgent need for innovative pancreatic islet transplantation procedures [7]. This is where stem cells (SCs) pose an important role.

SCs are a highly promising novel treatment for T1D due to their ability to differentiate into several cell types and their regenerative potential. SCs can be categorized into four basic groups based on their origin as shown in Figure 1.

Mesenchymal stem cells (MSCs), also called mesenchymal stromal cells, are non-hematopoietic, multipotent SCs. They can be extracted from a variety of sources, including bone marrow, liver, kidney, adipose tissue, urine, umbilical cord blood, umbilical tissue, Wharton's jelly, placenta, and even endometrial tissue (menstrual blood-derived endometrial stem cells - MenSC). Several surface markers, including CD73, CD90, and CD105, can be utilized to identify MSCs. Due to their ability to differentiate into numerous cell types, they can be used to repopulate damaged tissues [13,14]. MSCs have gained enormous popularity in the treatment of T1D because of their ability to regulate fibrosis and tissue regeneration, as well as their ability to modulate immunological function. In addition, they produce a variety of secretory molecules, such as cytokines and exosomes, which play an essential role in the treatment of T1D [15]. Studies on animals treated with MSCs have shown a significant reduction in hyperglycemia, as evaluated by a decrease in serum glucose and an increase in insulin and C-peptide levels. In addition, they were able to restore normal levels of lipid fractions. Using MSCs lowered the serum levels of both liver and kidney function markers in diabetic rats, demonstrating their hepato-renal protective benefits in T1D [16].

Several mechanisms have been discovered to play a role in the management of T1D by MSCs (Figure 2).

MSCs, such as bone marrow stromal cells, promote angiogenesis through the secretion of cytokines such as basic fibroblast growth factor and vascular endothelial growth factor (VEGF) [17]. In addition, they play a crucial role in immunomodulation by moving to areas of inflammation and modifying the phenotype of dendritic cells (DC), T cells, B cells, and natural killer cells. They downregulate proinflammatory cytokines and escape CD8+ T cell-mediated apoptosis, inhibit maturation of DC, while reducing T-lymphocyte proliferation via transforming growth factor-beta 1 (TGF-1), hepatocyte growth factor, and nitric oxide. By stimulating the production of regulatory T cells, TGF-1 plays a significant role in the immunomodulation of MSCs. MSCs have also been found to improve the function, survival, and graft outcome of neonatal porcine islets by increasing the expression of genes involved in the formation of endocrine cells, insulin, and platelet-derived growth factor alpha (PDGFR-). PDGFR- suppresses Notch 1 signaling (Notch 1 downregulates transcription factors involved in the formation of endocrine cells and insulin), resulting in the maturation and development of islet cells [18]. Zhou et al. discovered that wild-type p53-induced phosphatase 1 (a serine/threonine phosphatase) regulates the immunomodulatory properties of MSCs via the expression of interferon-alpha and bone marrow stromal cell antigen 2, consequently playing an important role in the therapeutic effects of MSCs in T1D [19].

Even though studies have shown that MSCs are capable of reconfiguring the immune system, they must be rescued to some extent from immune-mediated destruction, indicating that immunomodulation will be necessary even if a viable MSCs therapy for T1D is produced [20]. When using -cells from an allogeneic stem cell source, an alloreactive response to donor antigens will be generated unless we obtain SCs from the patient's own cells. To circumvent this, researchers have investigated encapsulation strategies employing semipermeable immune barriers to provide immune shielding and prevent graft rejection [21]. Some studies have also demonstrated that the use of suicide genes together with stem cell transplants promotes functional immune reconstitution and thereby prevents graft-versus-host disease in patients [22].

It has been demonstrated that MSCs undergo apoptosis in the circulation of the host or in engrafted tissues following delivery to the patient's body, which plays a significant part in their therapeutic role in T1D. During the execution of apoptosis, apoptotic extracellular vesicles (apoEVs), formerly known as apoptotic bodies, have emerged as regulators of numerous biological processes, as opposed to being only debris. Specifically, apoEVs have been shown to regulate T cell and macrophage immunological function as well as stimulate tissue repair, including skin regeneration and vascular protection [23].

This game-changing discovery of MSCs in the treatment of T1D has propelled biological sciences to a new level of sophistication, allowing for the manipulation of cell fate and the cultivation of higher-order cellular structures. However, there is still a huge gap regarding its application in actual clinical practice.

We were only able to find 12 clinical trials on PubMed that evaluated the use of MSCs in the treatment of T1D. Ten of the 12 studies were undertaken in Asia, primarily in China and India. To date, the exact pathogenesis of T1D is not fully understood. Genetic factors have been found to play a role in the development of T1D, which may have affected the outcomes of previous clinical trials. Therefore, conducting multiple different studies worldwide would not only enable us to identify the effects of ethnicity and genetics on the response to MSC therapy in T1D patientsbut also help us to generalize the efficacy of MSCs to the entire population. In order to achieve the best outcomes while using medications to treat T1D, it is also crucial to perform additional research to more clearly identify the pathophysiology of T1D.

In the course of studying the patient selection criteria utilized in clinical trials, we made a fascinating discovery. We found that every clinical study had excluded patients with immunosuppression, viral illnesses such as hepatitis B and C, comorbidities including hematologic diseases, rheumatologic diseases, and kidney diseases, and pregnant patients, all of which could have influenced the results of the studies. Our present understanding of the action of apoEVs, as described by Fu et al., leads us to believe that in order for MSCs to undergo apoptosis, their recipients must be able to initiate apoptotic activity [23]. In order for this to occur, patients must have a particular number of cytotoxic T cells or natural killer cells; hence, patients who do not meet this criterion are unlikely to benefit from MSC delivery. To further elucidate the mechanisms of action of MSCs, it is essential to undertake additional studies with immunosuppressed patients in order to identify the optimal cohort of T1D patients for MSC therapy. In addition, further clinical research should be conducted to uncover the apoptotic signals that stimulate tissue regeneration and angiogenesis, as recognizing these signals would allow us to utilize a channel in parenchymal tissue to increase its regeneration capacity.

We also observed that the majority of trials exclusively enrolled patients with recent-onset T1D. A study conducted in Iran revealed that early transplantation of MSCs resulted in superior outcomes for T1D patients compared to late transplantation. This may be due to the honeymoon phase of diabetes, which may have obscured the effects of MSCs in these studies [24]. The honeymoon phase is the period during which a person with T1D appears to improve and may only require minimal amounts of insulin or experience normal or near-normal blood sugar levels without insulin. To extrapolate the results to a larger population and unmask the effects of the honeymoon period, it is necessary to conduct trials on patients with late-onset T1D.

To date, the exact mechanism by which MSCs contribute to the remission of T1D has not been identified; therefore, further research is required to get a better knowledge of mechanisms such as immunomodulation, homing, and paracrine signaling of MSCs. It is also vital to undertake studies to discover the appropriate number of MSCs, injection frequency, and optimal infusion route in order to maximize results. Cai et al. concluded that pancreatic arterial transfusion would assist in avoiding the first pass pulmonary effect of MSCs, hence lowering the sequestration of MSCs in the lungs and allowing for optimal results [25].

A few studies have used 3D microspheres to increase the proliferation capacity of MSCs with positive results. However, there is insufficient information available regarding the proliferation capacity, revascularization, efficiency of differentiation, and survival time of MSCs. Therefore, conducting studies to elucidate these aspects of MSC therapy is an urgent necessity. We would also be able to learn more about the graft's survival time and tumorigenic potential if we followed the patients for a longer period of time.

Patient-specific variables such as age, body mass index, lifestyle, socioeconomic status, level of activity, diet, autoimmune status, and drug interactions must be taken into consideration while conducting studies and analyzing data. In order to identify the ideal conditions necessary to create the desired quantities of MSCs to achieve remission of T1D, future research must also incorporate in-depth information regarding external factors that affect the viability of MSCs, such as storage conditions, plating density, and culture media.

In this article, we aim to discuss the role of MSCsderived from various tissues in the treatment of T1D, as well as their feasibility and limitations.

We present a summary of the extraction methods, advantages, limitations, and outcomes from several studies of MSCs derived from various types of tissues.

The majority of umbilical cord tissue-derived stem cells (UC-MSCs) are found in the subcortical endothelium of the umbilical cord, the perivascular area, and Wharton's jelly [26]. According to studies, roughly1 106UC-MSC can be extracted from a 20 cm human umbilical cord [27]. MSCs isolated from Wharton's jelly have been grown for over 80 population doublings without showing any signs of senescence, morphological alterations, an increase in growth rate, or a change in their ability to develop into neurons. Recent research has demonstrated that xenotransplantation of post-differentiated human UC-MSC without immunosuppressive therapy does not result in rejection [28]. This lack of immunogenicity may be attributable to the absence of major histocompatibility II and co-stimulatory molecules such as CD80 (B7-1), CD86 (B7-2), and CD40 [29]. Chao et al. successfully differentiated human UC-MSC into clusters of mature islet-like cells with insulin-producing capacity. In the islet cells, they detected an increase in insulin and other -cell-related genes, including Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2. Moreover, they discovered that hyperglycemia in diabetic rats was greatly under control after xenotransplantation of human pancreatic islet-like cell clusters [28]. Patients with newly diagnosed T1D who received repeated intravenous doses of allogeneic UC-MSC showed improved islet cell preservation and a significant rise in postprandial C-peptide levels. However, C-peptide levels did not alter significantly in patients with juvenile-onset T1D. The number of UC-MSC contributed more than other indicators to the prediction of clinical remission, bolstering the evidence of dose-dependent therapeutic efficacy. Therefore, appropriate doses and courses of MSC transplantation should be granted importance in future research [30].

UC-MSC can also be used to treat chronic complications of T1D, such as neuropathy, DN, and retinopathy [31]. Studies have shown that intraperitoneal injection of human UC-MSC can ameliorate renal injury in streptozotocin-induced diabetic mice.[32]. A mice study conducted in China demonstrated that the combination of human UC-MSC and resveratrol can better protect renal podocyte function and the resulting reduction in blood glucose levels and renal damage is superior to those obtained with insulin administration [33]. This suggests that the combination of resveratrol and human UC-MSC may be an innovative technique for treating T1D; however, additional research on humans is necessary to determine the effects of this combination treatment on the management of DN.Another investigation involving mice revealed that UC-MSC therapy restored erectile function by suppressing toll-like receptor 4, alleviating corpora cavernosa fibrosis, and boosting the production of VEGF and endothelial nitric oxide synthase [34]. Nonetheless, a significant advantage of UC-MSC is that they are a rich source of many SCs that can be easily manipulated [27]. They are collected at delivery by clamping and severing the umbilical cord. There are no ethical concerns regarding the use of UC-MSC because the collecting process is non-invasive and retains material that would otherwise be discarded as waste.

Adipose tissue-derived mesenchymal stem cells (ADSCs) are a group of cells that arise from the mesoderm during embryonic development. Amongst several types, subcutaneous adipose tissue seems to be the most clinically relevant source, being available in abundance for harvest, and its isolation only slightly invasive [35,36].

While two major kinds of adipose tissue (white and brown) have been isolated and studied, we focus on white adipose, which produces ADSCs, as brown adipocytes have not yet demonstrated an association with insulin resistance. White adipose tissue expressing uncoupling protein 2 (an isoform of uncoupling protein 1in brown adipose) acts as a storage of excess energy in the form of triglycerides and is thus prone to causing obesity and abnormalities in metabolic pathways such as insulin resistance during hyperplasia [37].

The extracted cell group of interest consists of a putative stem cell population of fibroblast-like cells known as processed lipoaspirate (PLA), found within the stromal compartments of adipose tissue [38]. Obtaining the sample requires lipoaspiration, and although the technique does not negatively affect the function of ADSCs, the vacuum process involved can cause damage to mature adipocytes [37]. Studies have shown that successfully extracted PLA can then differentiate in vitro into multiple cell lineages (including adipogenic, myogenic, chondrogenic, and osteogenic cells), thus providing another source of SCs with multi-germ-line potential instead of the traditional bone marrow-derived MSCs [38-41]. The discovery of the ability of ADSCs to efficiently differentiate into IPC has shed new light on the approach to T1D management [41].

ADSCs utilization can help avoid ethical barriers and tumorigenic complications that are increasingly encountered during stem cell isolation from embryos and induced pluripotent SCs [36]. Yet another advantage of ADSCs for their therapeutic application happens to be the relatively painless procedure and high yields in harvested cell numbers compared to bone marrow procurement [40]. These cells are devoid of human leukocyte antigen-DR expression and therefore have been successfully transplanted via intravenous, intraperitoneal, and renal capsule administration in mice without the need for immunosuppression [36,42].

Insulin replacement therapy with the help of co-transplantation of insulin-secreting ADSCs has been studied as an alternative to lifelong insulin therapy. As with multiple studies, no adverse effects were observed with ADSCs infusion, and in fact, an impressive absence of DKA episodes in all participants was seen [43]. A prospective study conducted in 2015 on 20 patients with T1D found better diabetic control (hemoglobin A1c levels) and sustained improvements in fasting blood sugar, postprandial blood sugar, hemoglobin A1c, and C-peptide levels with the transplantation of autologous insulin-secreting ADSCs [44]. Dantas et al. concluded that combination therapy with ADSCs and Vitamin D (daily cholecalciferol for six months) without immunosuppression was safe, demonstrated immunomodulatory effects, and may play a role in -cell preservation in patients with newly diagnosed T1D [45]. The significant functional and morphological improvements in islet cells as early as two months after transplantation of IPC clusters derived from ADSCs point to the promising nature of this therapeutic approach for achieving target normoglycemia [46,47]. A recent study conducted in 2022 discovered that systemic administration of ADSCs protects male non-obese diabetic (NOD) mice against diabetes induced by programmed death-1 and programmed death-ligand 1 (PD-1/PD-L1) inhibition. Multiple injections of neutralizing antibodies against mouse PD-L1 induce a significant infiltration of immune cells in the islets and a decrease in the -cell area and insulin content of the pancreas. Despite this, systemic ADSCinjection partially protected the pancreas from -cell loss and preserved insulin content, indicating therapeutic potential in T1D [15].

Apart from the therapeutic uses in T1D, the ADSCtherapy has also been shown to reduce adverse effects brought about by complications such as DN and ESRD [48,49]. Inactivation of nuclear factor kappa B pathways and downregulation of VEGF-A, amongst others, are the major mechanisms involved in ameliorating the pathological manifestations of mice with DN [50].

The problem remaining, however, is the inability to become totally free of exogenous insulin. Research suggests that a much larger dose of IPC may be required for a sustained cure of T1D using ADSCs [51]. Therefore, the need of the hour is to conduct further research, placing emphasis on ways to either enhance the production of insulin in IPC derived from ADSCs or alter cell signaling pathways to obtain a greater number of IPC from ADSCs.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are a type of adult stem cell that is abundant in bone marrow and has low immunogenicity [52]. Bone marrow stem cells are broadly categorized into hematopoietic stem cells and MSCs. These cells are sourced from the same individual, potentially minimizing rejection problems and making it a form of therapy for T1D [53]. BM-MSCs can differentiate into functionally competent -cells in vivo, and NOD mouse studies have shown the formation of normal T cell and B cell function, implying that allogeneic bone marrow transplant could prevent islet destruction and restore self-tolerance [54,55]. Because of their well-documented hypoimmunogenic and immunomodulatory properties, BM-MSCs are an appealing therapeutic option for T1D [56].

One study looked at T1D patients with DKA and found BM-MSCs to preserve -cell function in T1D patients, reducing levels of fasting and post-prandial C-peptide levels, with one patient achieving insulin independence for a period of three months [57].

BM-MSCs have been demonstrated to mitigate the effects of metabolic and hepato-renal abnormalities, enhance lipid profiles, and improve carbohydrate and glycemic management. Following an eight-week period of injections with BM-MSCs in diabetic rats, an improvement was observed in their lipid profiles compared to diabetic rats that were not treated with BM-MSCs [16]. In addition, BM-MSCs therapy has been demonstrated to ameliorate diabetes-related liver damage by boosting endogenous hepatocyte regenerative mechanisms and enhancing liver function [58].

BM-MSCs have also been shown to effectively treat comorbidities of T1D, such as DN, poor wound healing, and erectile dysfunction (ED). Nagaishi et al. investigated a novel approach of mixing BM-MSCs with umbilical cord extracts in Wharton's Jelly to enhance the therapeutic effect of ameliorating renal injury in T1D patients with DN. The study demonstrated morphological and functional improvements of diabetes-derived BM-MSC in vitro and a therapeutic impact on DN in vivo, suggesting that this may be beneficial not only for patients with DN but also for patients with other diabetic complications [59]. One study looked to address the problem of impaired epithelial wound healing in T1D patients and found that BM-MSCs promote corneal epithelial wound healing via tumor necrosis factor-inducible gene 6-dependent stem cell activation [60]. Another promising phase I pilot clinical trial found that treating ED in T1D patients with two consecutive intracavernous injections of autologous BM-MSC was safe and effective [61].

Currently, several potential therapeutic approaches are being postulated to approach this issue of T1D from a new viewpoint. Suicide gene therapy is a strategy with potential. This method involves the introduction of suicide-inducing transgenes into the body via BM-MSC. As a result, several processes will be induced, including the suppression of gene expression, the production of intracellular antibodies that block the essential pathways of cells, and the transgenic expression of caspases and deoxyribonucleases. Current clinical trials are examining strategies to restore damaged organs with the use of stem cells as the delivery mechanism [62].

The idea of transplanting BM-MSCs provides patients with hope. Particularly significant are autologous BM-MSC (which are easy to obtain and avoid graft rejection after transplantation) in contrast to allogeneic BM-MSC transplantations, which may result in graft rejection and be accompanied by complications [52]. For stem cell therapy to be most beneficial, early delivery of stem cells following a diagnosis of T1D is necessary compared to intervention at later stages [63].

Table 1compares the properties of MSCs derived from the bone marrow, umbilical cord, and adipose tissue.

Recent research has demonstrated that menstrual blood-derived endometrial stem cells (MenSCs) have therapeutic promise for the treatment of T1D due to their exceptionally high rates of proliferation, noninvasive collection method, and significant immunomodulatory activity. In T1D model mice, MenSC and UC-MSC transplantation resulted in a significant decrease in blood glucose and insulin levels, as well as an improvement in the morphology and function of the liver, kidneys, and spleen [14]. A 2021 study found that MenSCs expressed pancreatic -cell genes such as INSULIN, GLUT-2, and NGN-3 and had a greater capacity to develop into pancreatic cells [64].

Dental pulp-derived mesenchymal stem cells (DP-MSCs) are one of the unique MSCs proposed for the treatment of T1D. DP-MSCs are derived from exfoliated human deciduous teeth and have the properties of being easy to obtain with minimal donor injury. In a study by Mo et al. DP-MSCs revealed the ability to differentiate into pancreatic -cells; nevertheless, before proceeding with larger-scale investigations to firmly establish this approach, it is necessary to devise procedures for optimal -cell differentiation in-vivo [65].

An in-vivo study revealed that conjunctiva-derived mesenchymal stem cells (C-MSCs) efficiently differentiated into pancreatic islet stem cells in 2D cultures and 3D scaffolds under optimal induction conditions. C-MSCs have a strong proliferative capacity, a spindle shape, a high potential for clonogenic differentiation, and are widely available. However, larger in vitro studies are necessary before C-MSCs can be deemed an established treatment for T1D [64].

Table 2 lists all clinical trials that have utilized MSCs in the treatment of T1D and complications related to T1D (Table 2).

Our article relies on a survey of free full-text research journals over the past decade; consequently, it is possible that we have omitted pertinent information from paid full-text as well as research articles published prior to 2010.In addition, the scope of this study is confined to studies in the English language, so we may have overlooked papers published in other languages.

MSCs are postulated to act in T1D and numerous other disorders through diverse mechanisms. Among these are homing and immunomodulation. Our review revealed that MSCs not only effectively reduce fasting blood sugar, C-peptide, and hemoglobin A1c levels but are also capable of treating microvascular complications associated with T1D. However, the specific pathophysiology of T1D diabetes is still unknown, making it difficult to develop novel treatments. To achieve remission of T1D, we must also consider the effects of additional factors on the efficacy of MSCs, including patient-specific variables such as age, body mass index, lifestyle, socioeconomic status, level of activity, diet, autoimmune status, and drug interactions, as well as external factors such as storage conditions, plating density, and culture media. Therefore, it is urgent to conduct larger-scale studies.

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The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes - Cureus

Bone Marrow Stem Cells Comments Off on The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes – Cureus | August 2nd, 2022

CASE SUMMARY

A 54-year-oldwoman presented with Revised International Staging System stage II multiple myeloma, based on evaluations that showed a hemoglobin level of 7.0 g/dL, 2-microglobulin of 6 mg/dl, albumin 3.2 g/dL, calcium 11.3 mg/dL, lactate dehydrogenase of 200 U/L, and creatinine clearance of 45 mL/min. Bone marrow showed 22% clonal plasma cells. Serum kappa free light chains were 24 mg/dL. She had no cytogenetic abnormalities and an ECOG performance score of 1. A PET/CT scan showed multiple bone lesions in the vertebrae. She had no extramedullary disease. She was diagnosed with IgG-kappa myeloma and was considered transplant eligible.

Daratumumab (Darzalex), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Dara-VRd) induction therapy was initiated. She achieved a very good partial response (VGPR) post induction therapy. She underwent stem cell mobilization and 2 months later underwent autologous stem cell transplant (ASCT). Her post-ASCT response was a VGPR.

DISCUSSION QUESTIONS

CAITLIN COSTELLO, MD: This patient did get a quadruplet regimen with dara-VRd. She achieved a VGPR post-induction, had stem cells mobilized, underwent her transplant, and post-transplant her response is a VGPR. What would you do next?

THOMAS DEKKER, MD: Consolidation with CAR [chimeric antigen receptor] T-cell therapy.

COSTELLO: With CAR T cell, sure. Youre going for it; I like it. This patient is post-transplant, they have a VGPR. The GRIFFIN study [NCT02874742] would give these patients consolidation with dara-VRd.

PREETI CHAUDHARY, MD: I would not do CAR T-cell therapy.

COSTELLO: What would you do?

CHAUDHARY: In my opinion, in multiple myeloma, patients do a maximum of 11 months with CAR T-cell therapy. It has a good response, but I dont think thats sustainable.

COSTELLO: I appreciate throwing ideas out there. That is not something we have an option to do right now. Its an interesting option, and something we can talk about; but yes, I agree with you. I think for the meantime, short of trials that are looking at doing CAR T-cell therapyparticularly for those patients who have not had an adequate response to transplant or consolidation, or patients who relapse shortly after their transplantI think the standard of care as it stands now is doing consolidation or trying to find a maintenance regimen to get them to minimal residual disease [MRD] negativity.

With all that being said, what are we going to do now for these patients? Weve talked about what these transplant eligible patients are getting consolidation and maintenance; weve talked about maintenance approaches for these patients who get quadruplets, to put them on doublets. Seeing all those deep response rates, is anyone getting cold on transplants? If we are going to get 90% remission rates, does anyone reconsider the role of transplant here?

PAMELA MIEL, MD: I dont make that call, meaning I still send patients to the transplant doctors to see if theyre going to proceed with the transplant or not. But, if theyre transplant eligible, they get referred.

COSTELLO: As a transplanter, I thank you for that. We want to see these patients, make the decisions, have the discussion with the patients so we can look at their risk/benefit profile, and understand their responses to their current therapy. So, please still send them in their third cycle, if not earlier, so we can have those discussions and make plans.

There are a lot of maintenance regimens that are out there, and different things to choose from; a whole other conversation in and of itself. Lenalidomide is the mainstay where we have an overall survival benefit, where we dont have it in any other maintenance regimens.1 But it does allow for the option of continued doublets. I think we will soon see daratumumab and lenalidomide as a doublet get added on to that maintenance therapy once we have some of these randomized trials that are going on that show the continued benefit of patients to get daratumumab in the maintenance setting if they did not receive it in the up-front setting.

DISCUSSION QUESTION

How likely are you to change your practice with respect to management of transplant eligible newly diagnosed myeloma?

DEKKER: I already use quadruplet.

MILAN SHETH, MD: I feel that we still need a lot of long-term data to get a better sense of what it is that were achieving with the quadruplet therapy. Im still not convinced everybody needs quadruplet therapy. I think somebody else had already said that we know were going to get better responses because were using great drugs, but do we need to use everything up-front? I feel like theres still a lot of unanswered questions here.

MIEL: Ive been wanting to put patients on quadruplet treatment. I dont know if you know Nina Shah, MD, over at UC San Francisco, but Ive attended some of her talks, and shes pushing for the quadruplet treatment. The only thing that changed my mind was that when I spoke to the transplant doctor at UC San Diego, he said, If its not very high-risk disease, Id go with VRd [bortezomib, lenalidomide, and dexamethasone]. So, I put the patient on VRd. But I probably would want to put someone on dara-VRd, given the chance.

COSTELLO: Yes. I think that my takeaway from the data has been that we would, of course, love long-term data to come out, butwe have to wait a long time for it. While were waiting for some of these phase 3 studies to go on, which are happening now to look at real randomized data, to play out, I find that this is just too intriguing to not do quadruplets for everybody now.

Since [these data were presented at [the 2021 American Society of Hematology annual meeting], Ive transitioned just about everyone whos at least transplant eligible over to quadruplet regimens now.2 Any patients who are on the fence, where Im not sure if theyre going to be eligible for transplant, I still will try and give them the benefit of a quadruplet regimen, and very quickly drop the bortezomib if I get worried about them, and end up with dara-Vd [daratumumab, lenalidomide, dexamethasone]. But I think these MRD negativity rates are just too good, and if that is going to be the true surrogate end point that were all aiming for, dara-VRd has been my go-to for the last 6-plus months or so for these patients, until someone tells me otherwise.

References

1. Ho M, Zanwar S, Kapoor P, et al. The effect of duration of lenalidomide maintenance and outcomes of different salvage regimens in patients with multiple myeloma (MM).Blood Cancer J. 2021;11(9):158. doi:10.1038/s41408-021-00548-7

2. Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): updated analysis of GRIFFIN after 24 months of maintenance. Blood. 2021;138(Suppl_1):79. doi:10.1182/blood-2021-149024

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Treating Multiple Myeloma Following Quadruplet Induction Therapy and ASCT - Targeted Oncology

Bone Marrow Stem Cells Comments Off on Treating Multiple Myeloma Following Quadruplet Induction Therapy and ASCT – Targeted Oncology | August 2nd, 2022

Researchers have revealed the cellular mysteries behind aging.

A new explanation for aging has been developed by researchers who have shown that genetic abnormalities that develop gradually over a lifetime cause substantial alterations in how blood is generated beyond the age of 70.

According to recent research, the drastic reduction in blood production beyond the age of 70 is likely caused by genetic alterations that steadily accumulate in blood stem cells throughout life.

Researchers from the Wellcome Sanger Institute, the Wellcome-MRC Cambridge Stem Cell Institute, and others have published a study that offers a new theory of aging in the journal Nature.

Somatic mutations, or alterations to the genetic code, occur in all human cells during the course of a lifetime. Aging is most likely caused by the accumulation of numerous sorts of damage to our cells over time, with one hypothesis proposing that the accumulation of somatic mutations causes cells to gradually lose functional reserve. However, it is still unknown how such slow-building molecular damage may result in the rapid decline in organ performance around the age of 70.

The Wellcome Sanger Institute, the Cambridge Stem Cell Institute, and collaborators examined the production of blood cells from the bone marrow in 10 people ranging in age from newborns to the elderly in order to better understand how the body ages.

3,579 blood stem cells had their whole genomes sequenced, allowing researchers to determine every somatic mutation present in each cell. Using this information, the team was able to create family trees of each persons blood stem cells, providing for the first time an impartial perspective of the connections between blood cells and how these ties develop over the course of a persons lifetime.

After the age of 70 years, the researchers discovered that these family trees underwent significant change. In adults under the age of 65, 20,000 to 200,000 stem cells contributed roughly equal amounts to the creation of blood cells. In contrast, blood production was exceedingly uneven in those above the age of 70.

In every elderly person investigated, a small number of enlarged stem cell clonesas few as 10 to 20contributed as much as half of the total blood output. Because of an uncommon class of somatic mutations known as driver mutations, these highly active stem cells have gradually increased in number during that persons life.

These findings led the team to propose a model in which age-associated changes in blood production come from somatic mutations causing selfish stem cells to dominate the bone marrow in the elderly. This model, with the steady introduction of driver mutations that cause the growth of functionally altered clones over decades, explains the dramatic and inevitable shift to reduced diversity of blood cell populations after the age of 70. Which clones become dominant varies from person to person, and so the model also explains the variation seen in disease risk and other characteristics in older adults. A second study, also published in Nature, explores how different individual driver mutations affect cell growth rates over time.

Dr. Emily Mitchell, Haematology Registrar at Addenbrookes Hospital, a Ph.D. student at the Wellcome Sanger Institute, and lead researcher on the study, said: Our findings show that the diversity of blood stem cells is lost in older age due to positive selection of faster-growing clones with driver mutations.

These clones outcompete the slower-growing ones. In many cases this increased fitness at the stem cell level likely comes at a cost their ability to produce functional mature blood cells is impaired, so explaining the observed age-related loss of function in the blood system.

Dr. Elisa Laurenti, Assistant Professor and Wellcome Royal Society Sir Henry Dale Fellow at the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge, and joint senior researcher on this study, said: Factors such as chronic inflammation, smoking, infection, and chemotherapy cause earlier growth of clones with cancer-driving mutations. We predict that these factors also bring forward the decline in blood stem cell diversity associated with aging. It is possible that there are factors that might slow this process down, too. We now have the exciting task of figuring out how these newly discovered mutations affect blood function in the elderly, so we can learn how to minimize disease risk and promote healthy aging.

Dr. Peter Campbell, Head of the Cancer, Ageing and Somatic Mutation Programme at the Wellcome Sanger Institute, and senior researcher on the study said: Weve shown, for the first time, how steadily accumulating mutations throughout life lead to a catastrophic and inevitable change in blood cell populations after the age of 70. What is super exciting about this model is that it may well apply to other organ systems too. We see these selfish clones with driver mutations expanding with age in many other tissues of the body we know this can increase cancer risk, but it could also be contributing to other functional changes associated with aging.

References: Clonal dynamics of haematopoiesis across the human lifespan by Emily Mitchell, Michael Spencer Chapman, Nicholas Williams, Kevin J. Dawson, Nicole Mende, Emily F. Calderbank, Hyunchul Jung, Thomas Mitchell, Tim H. H. Coorens, David H. Spencer, Heather Machado, Henry Lee-Six, Megan Davies, Daniel Hayler, Margarete A. Fabre, Krishnaa Mahbubani, Federico Abascal, Alex Cagan, George S. Vassiliou, Joanna Baxter, Inigo Martincorena, Michael R. Stratton, David G. Kent, Krishna Chatterjee, Kourosh Saeb Parsy, Anthony R. Green, Jyoti Nangalia, Elisa Laurenti, and Peter J. Campbell, 1 June 2022, Nature.DOI: 10.1038/s41586-022-04786-y

The longitudinal dynamics and natural history of clonal haematopoiesis by Margarete A. Fabre, Jos Guilherme de Almeida, Edoardo Fiorillo, Emily Mitchell, Aristi Damaskou, Justyna Rak, Valeria Orr, Michele Marongiu, Michael Spencer Chapman, M. S. Vijayabaskar, Joanna Baxter, Claire Hardy, Federico Abascal, Nicholas Williams, Jyoti Nangalia, Iigo Martincorena, Peter J. Campbell, Eoin F. McKinney, Francesco Cucca, Moritz Gerstung, and George S. Vassiliou, 1 June 2022, Nature.DOI: 10.1038/s41586-022-04785-z

The study was funded by Wellcome and the William B Harrison Foundation.

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Scientists Unlock the Secrets of Cellular Aging: What Happens After You Turn 70? - SciTechDaily

Bone Marrow Stem Cells Comments Off on Scientists Unlock the Secrets of Cellular Aging: What Happens After You Turn 70? – SciTechDaily | August 2nd, 2022

For those with cancer, the threat of serious illness from COVID-19 is often a major concern. Cancer treatments can weaken your bodys immune system, increasing your risk of a serious infection.

Immunotherapy is a type of cancer treatment that boosts and supports your immune system in responding against cancer. If you or a loved one is receiving immunotherapy treatment for cancer, you may have concerns about how the COVID vaccine may affect your immune system and your treatment.

This article will answer some common questions about immunotherapy cancer treatment and the COVID vaccines.

People with a weakened immune system due to cancer are at an increased risk for poor outcomes from COVID-19. No matter where you are in your treatment plan, vaccination can reduce your risk of developing severe COVID. Vaccination is important even for those with a robust immune system.

The National Comprehensive Cancer Network (NCCN) and the American Cancer Society recommend that people with cancer, including those receiving treatment, get vaccinated as soon as possible. NCCN notes a few exceptions regarding immediacy:

Since they weaken the immune system, some cancer treatments reduce but dont eliminate vaccine effectiveness. Even if youre getting one or more of these treatments, you will gain some protection from the vaccine. Treatments include:

Vaccination combined with protective measures, such as wearing a mask and avoiding large crowds, provides you with more protection from COVID than you would have without them. For that reason, experts strongly recommend vaccination for people with cancer or a history of cancer.

But check with your oncologist first about when you should get vaccinated. If you are currently receiving treatment for cancer, it may be best to wait until your immune system recovers from treatment. This will give you the best chance of mounting a strong immune response.

Both the Pfizer BioNTech and the Moderna mRNA vaccines are appropriate for use in people who take immunotherapy drugs. Neither vaccine is known to be better than the other for this population.

A 2021 study found that the Moderna vaccine was safe for people with solid tumors receiving chemotherapy, immunotherapy, or both. Their response to the vaccine was similar to those who did not have cancer. The groups also saw similar rates of side effects.

A separate 2021 study noted that people with solid tumors who had the Pfizer vaccine had similar antibody levels to those without cancer 6 months after vaccination. In the subgroup of people on immunotherapy, about 87% still had antibodies, compared to about 84% of the control group.

If you cannot get or do not want either of these vaccines, you can also get the Johnson & Johnson (Janssen) vaccine.

Having cancer or taking immunotherapy drugs does not increase the possibility of serious side effects, such as allergic reactions or myocarditis.

Swelling in the lymph nodes under the arm on the same side as the injection site is a potential side effect of vaccination. While temporary, this can be concerning for people with breast cancer and other cancers.

Tenderness and swollen lymph nodes caused by vaccination should subside within a few days to a few weeks. Let a healthcare professional know if the swelling increases or does not go away within this timeframe.

To date, researchers do not know definitively if immunotherapy drugs affect the effectiveness of COVID-19 vaccines, either positively or negatively.

Scientific articles from 2021 and 2022 suggest that checkpoint inhibitors could theoretically boost your immune response to the COVID-19 vaccine. But both articles also state that no study has demonstrated such an effect.

Some immunotherapy drugs, such as CAR T-cells, may weaken the immune system temporarily. This may make the vaccine less effective. Other types of immunotherapy drugs, such as monoclonal antibodies, should not have this effect.

People with compromised immune systems may find it difficult to generate a robust response to the vaccine, no matter what type of cancer treatment they receive. This may be particularly true for people with blood cancers. For that reason, dosing protocols for people who are immunocompromised and have cancer differ from those used for the general public.

To date, no data indicate that the COVID vaccine reduces the effectiveness of immunotherapy medication. But there may be a 17% to 48% risk of side effects due to an overstimulated immune response, according to research.

A case report published in May 2021 suggests the potential for cytokine release syndrome after COVID vaccination in patients taking certain immunotherapy drugs. The study authors state that more data is needed and still favor vaccination for people with cancer.

A 2021 study involving 134 people found no adverse effects from immunotherapy drugs after receiving the Pfizer vaccine. The studys authors also stressed the need for larger studies and more data, but supported vaccination for people receiving immunotherapy.

However, the impact of certain immunotherapy treatments on your immune system makes the timing of vaccination important. Talk with your oncologist about when you should schedule your vaccine.

People taking immunotherapy drugs should receive an additional primary dose of the vaccine if they have active cancer or are immunocompromised. You may fall into one of these categories if any of the following situations apply:

Yes. Getting COVID does not ensure you will not get it again. In fact, with ever-changing variants continually emerging, contracting the virus more than once has become commonplace.

If youre on cancer treatments that cause you to be immunocompromised, it is vital to get vaccinated, even if youve already had COVID. Talk with your oncologist about when you should get vaccinated after having COVID-19.

If you have cancer, you may be more likely to experience serious complications from COVID-19. Cancer treatments, including certain immunotherapy drugs, may affect your scheduling for vaccination. Talk with your oncologist about when you should schedule your vaccines and how many doses you should get.

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Immunotherapy and COVID Vaccine: Your Questions Answered - Healthline

Bone Marrow Stem Cells Comments Off on Immunotherapy and COVID Vaccine: Your Questions Answered – Healthline | August 2nd, 2022