Louise Herbert flew more than 8,000 miles in January for a risky procedure to slow her MS and says its the best thing shes ever done.

The 41-year-old mum, originally from Shetland, had been a keen runner and netball player before she was diagnosed with the condition at 26.

It caused her immune system to attack itself, at times leaving her so exhausted she could barely spend time with her nine-year-old daughter.

At the start of the year Louisetravelled from her home in Newmachar, Aberdeenshire to Puebla, Mexico for 47,000 haematopoietic stem cell transplantation (HSCT).

Some patients find it does more harm than good causing hair loss, nausea and even infertility and around 3% die from the treatment.

But Louise felt it was a risk worth taking.

During the treatment, doctors took stem cells from Louises bone marrow.

Then used intense chemotherapy to wipe out her immune system, before reintroducing the cells to try and reset her body.

Although Louise did suffer excruciating back pain during her treatment, shes relieved she dodged many of the other side effects.

To be honest, I think I was really lucky because the chemotherapy never made me feel sick, I never felt nauseous or lost my appetite, she explained.

The only thing that really bothered me was these injections we got every morning and every night for a week.

I got horrendous back pain one night, it was so bad I pressed the SOS button on the phones we had to speak to a doctor, she recalled.

Though the back pain was an unpleasant experience, from a medical point of view it was actually a positive.

She said: It was showing there was plenty of stem cells there and they were ready to come out, I think they came out two days later.

One effect of the chemo was that Louises hair fell out but its started to grow back with wild and frizzy curls.

I dont think Ill grow it much beyond my chin, she added.

Though its still too early to be certain, Louise believes there have already been some encouraging signs.

She said: Its still early days, they say its 12 to 18 months before any improvements are seen. Im at seven-and-a-half.

I dont think I can walk any further than before, but I have a bit more confidence in my walking.

I went on the same walk seven times last week, I used to come home and the first thing I wanted to do was sit down in the chair, I wasnt like that last week.

Tasks such as putting on trousers also seems to be less strenuous for Louise than before.

She explained: It was a case I had to lift my left leg up because it couldnt lift itself, its been like that for about five years.

But for the past week Ive noticed I could lift it myself, Ive been going to Pilates which should help improve my balance.

I dont know if its that or the HSCT, but somethings done it.

Im not saying I can lift my leg every day, but if I can do it even three out of seven, thats great.

Upon reflection, Newmachar mum Louise is happy she made the decision to travel to Mexico for this MS treatment.

Im so glad I did it, its the best thing I ever did, youve got to try, she added.

Aberdeen woman with MS to spend 46,000 for stem cell treatment

Aberdeenshire mum says 8,000 mile Mexico trip is only option for her incurable condition

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'Best thing I ever did': Newmachar mum showing promising signs after 47000 MS treatment in Mexico - The Press & Journal

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Five people with the autoimmune condition lupus are now in remission after receiving a version of CAR-T therapy, which was originally developed for cancer

By Clare Wilson

Illustration of a CAR-T cell

CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY

A high-tech cell therapy used to treat cancer has been repurposed as a treatment for lupus, an autoimmune condition that can cause joint, kidney and heart damage.

CAR T-cell therapy has put all five people with lupus treated so far into remission. The participants have been followed up for an average of 8 months, with the first person treated 17 months ago. Thats kind of unheard of, says Chris Wincup at Kings College London, who wasnt involved in the study. This is incredibly exciting.

But it is too soon to know how long the remissions will last, says Georg Schett at the University of Erlangen-Nuremberg in Germany, who was part of the study team.

CAR T-cells were developed to treat blood cancers that arise when B cells, a type of immune cell that normally makes antibodies, start multiplying out of control.

The approach requires taking a sample of immune cells from a persons blood, genetically altering them in the lab so they attack B cells and then infusing them back into the individuals blood. It seems to put 4 out of 10 people with these kinds of cancers into remission.

Lupus, also called systemic lupus erythematosus, is caused by the immune system mistakenly reacting against peoples own DNA. This is driven by B cells making antibodies against DNA released from dying cells.

It is currently treated with medicines that suppress the immune system or, in more severe cases, with drugs that kill B cells. But the treatments cant kill all the B cells, and if the disease flares up badly, some people develop kidney failure and inflammation of their heart and brain.

Schett and his team wondered whether using CAR T-cells to hunt down all the B cells would be more effective. Within three months of receiving the treatment, all five participants were in remission, without needing to take any other medicines to control their symptoms.

The CAR T-cells were barely detectable after one month, and after three and a half months, the volunteers B cells started to return, having been produced by stem cells in bone marrow. These new B cells didnt react against the DNA.

We dont know what normally causes B cells to start reacting against DNA in people with lupus, so it is possible that some kind of trigger may start the process happening again, says Wincup.

The achievement means CAR T-cells may also be useful against other autoimmune diseases that are driven by antibodies, such as multiple sclerosis (MS), in which the immune system attacks nerves, says Schett.

Another radical treatment for MS involves rebooting the immune system by destroying it with chemotherapy. By comparison, CAR T-cells would be less invasive and more tolerable, he says.

But it is too soon to know how effective CAR T-cells will be for autoimmune conditions, says Wincup. This is a small number of patients, so we dont know if this is going to be the result for everyone.

When used in cancer, CAR T-cells are expensive to create for each person, so they may only be used for autoimmune conditions in people with severe disease when no other treatments are available, he says.

Journal reference: Nature Medicine , DOI: 10.1038/s41591-022-02017-5

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Introduction:Aplastic anemia (AA)is characterized by pancytopenia and hypocellular marrow in the absence of an abnormal infiltrate or increase in reticulin fibrosis. The diagnosis of AA is challenging at times due to decreased cellularity and overlapping morphological features with other bone marrow failure syndromes. Hepatitis-associated aplastic anemia (HAAA) is a rare variant in which patients typically present with jaundice and hepatitis followed by pancytopenia almost within 6 months. Post-hepatitis AA accounts for approximately 1-5%of cases, and invariably such cases are negative for the known hepatitis virus as well. There is limited literature available to understand the correlation of AA with hepatitis with none reported at the national level in our region. As AA is relatively more prevalent in Southeast Asia as compared to the western world and hepatitis is a prevalent disease in our population, the main purpose of this study was to assess the hepatic profile and determine the association of hepatitis in AA at the time of diagnosis.

Materials and methods:A cross-sectional study was carried out at the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, from November 2019 to December 2020 after the informed consent from patients. The study included all treatment-nave patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Liver function tests, complete blood count, prothrombin time (PT), and activated partial thromboplastin time were performed, along with viral profiles (HAV, Hep B, Hep C, and HIV). SPSS version 23 (IBM Corp., Armonk, NY) was used for statistical analysis. Mean and standard deviations were computed for quantitative variables while percentages and frequencies were reported for qualitative variables. T-test was used to observe the main difference between groups and a p-value <0.05 was considered to be significant.

Results:Out of a total of 351 patients, 29 (8.2%) patients with AA tested positive for viral hepatitis. Hepatitis A was the most prevalent hepatitis (4.0%), followed by hepatitis C (3.7%). The comparison of platelet counts in patients with and without hepatitis was reported to be of statistical significance (p-value < 0.05). A significant statistical difference (p-value< 0.0001) was found in platelet count and PTin patients of AA with and without hepatitis.

Conclusion:Overall, this study revealed that <10% of patients of AA had a positive screening for hepatitis A, B, and C and low platelet count, and PT was statistically significant when compared between the patients with and without hepatitis. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients with AA should be screened for liver functions and viral hepatitis at the time of diagnosis. In addition to hepatitis A, B, and C and HIV, other causes of hepatitis should also be screened such as parvovirus B19, human herpes virus 16, and adenovirus which are not included in routine diagnostic viral testing panel.

The distinctive manifestation(s) of aplastic anemia (AA) are pancytopenia and hypocellular bone marrow without evidence of infiltration, dysplasia, and fibrosis. It is caused by several risk factors including infections, toxins, chemotherapeutic drugs, and radiation but the precise cause remains unclear [1]. An uncommon form of AA known as hepatitis-associated aplastic anemia (HAAA) occurs when pancytopenia develops simultaneously with or within six months after an elevated serum alanine aminotransferase (ALT) level. Significantly, these ALT levels are five times higher than the upper limit of normal. Post-hepatitic AA accounts for approximately 1-5% of cases invariably, and such cases are negative for the known hepatitis virus as well [2].When compared to patients with non-hepatitis-associated AA in the pediatric population, those with HAAA have considerably lower survival and prognosis [3]. Hepatitis symptoms linked to HAAA can be self-limiting, but sometimes showmoderate to severe or acute to the chronic clinical course[4]. Necrosis of the portal region and fibrosis that extends up to the centrilobular area can be found in the transjugular liver biopsy of HAAA patients and chronic severe hepatic inflammation quickly progresses to liver fibrosis [5]. First-line therapies include stem cell transplantation from a sibling donor who matches the patient's human leukocyte antigen (HLA) profile or immunosuppressive therapies like cyclosporine and/or antithymocyte or antilymphocyte globulin [6,7].

The exact etiology of hepatitis causing AA is nearly unknown and the pathogenesis of HAAA has been associated with activated T1 cells [8]. Hepatitis B and C virus, parvovirus B19, human herpes virus 16, and transfusion-transmitted virus (hepatitis B, C, HIV) can all be causal associations. The traits include CD8+-predominant lobular necroinflammatory and endothelial damage associated with sinusoidal obstruction syndrome, conjugated hyperbilirubinemia, elevated antinuclear antibody titers, and elevated transaminases [9]. Dietary or nutrition supplements at times may also result in toxin-induced hepatitis [10].It is typical for intrabiliary cholestasis and liver toxicity to result in the apoptotic killing of hematopoietic cells by CD8 lymphocytes and T cell-induced gamma interferon, which leads to hepatitis. Clinical symptoms include pallor, exhaustion, petechial rash, and infections due to pancytopenia [11]. When severe thrombocytopenia and anemia appear at the same time as HAAA, it is important to distinguish this condition from infantile giant cell hepatitis with autoimmune hemolytic anemia [12].

Allogeneic bone marrow transplantation (allo BMT) is the conventional curative treatment for HAAA from an HLA-matched donor. Since HAAA has a poor prognosis, allo BMT has been the curative form of treatment [13-15]. On the other hand, immunosuppressive medication results in a response rate of 70% and a survival rate of 85% for patients not receiving hematopoietic cell transplantation, respectively [16]. Children respond to BMT better than adults do, and the survival rates of patients receiving bone marrow from HLA-matched donors are found to be comparable to that of the patients with AA not caused by hepatitis [17]. There is no recognized antiviral medication for hepatitis B-related HAAA. Lamivudine, a nucleoside analog, has been studied for use in treating hepatitis B-related HAAA, and it has been shown to be effective in causing remission in cases of severe AA and hepatitis B virus infection. Because of its myelosuppressive effects, interferon, an acclaimed antiviral agent in the treatment arsenal of HBV- and HCV-mediated infections, cannot be used as a treatment option for the HAAA [18]. Patients with HAAA exhibit severe pancytopenia following an episode of acute hepatitis, and if left untreated, the marrow suppression is frequently swift and severe.

In Pakistan, cases of hepatitis have been increasing over time, and given the current policies and practices, eradicating hepatitis from Pakistan by 2030 seems unreasonable[19]. We have also noted a rising trend in the incidence of AA than reported internationally. The association of hepatitis with AA is underreported and limited literature is available regarding the determinants of AA. Hepatitis might be one of the causes of AA and it must be considered an alarming situation.The only curative option for AA is BMT, which is an unaffordable treatment option for many patients in Pakistan. Therefore, the aim to conduct this study was to evaluate the hepatic status in relation to hepatitis in treatment-nave AA patients.

This was a cross-sectional study carried out at the National Institute of Blood Diseases and Bone Marrow Transplantation (NIBD & BMT). Patients were recruited between November 2019 and December 2021. Prior to the initiation of the study, approval was taken from the NIBD ethics committee bearing NIBD/RD-188/11-2019 and informed consent was taken from the participants prior to enrollment in the study. The study included all treatment-nave patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Patients with positive chromosomal breaks (Fanconis anemia) or inherited bone marrow failure were excluded. WHO sample size calculator was used to calculate the sample size, and by taking the percentage reported in the literature (5%) [14] it was found to be at least 73, and hence we recruited 351 patients who visited during the study duration.Non-probability purposive sampling method was used for patient selection. Demographicand laboratory parameters were recorded through a structured questionnaire and the diagnosis of AA was confirmed on bone marrow biopsy. Liver function tests (LFTs), complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (APTT) were performed. PT and APTT were run on STAGO and Sysmex CA-1500, and CBC was performed using a Sysmex XN-1000 analyzer from the Sysmex Corporation in Kobe, Japan. LFTs were performed on a Cobas C 111 analyzer machine that runs on a spectrophotometer principle.Within 2 hours of the blood sample collection, an aseptic setting was used to take a 4 ml blood sample from each patient, which was then tested for the presence of hepatitis A, HBV, HCV, and HIV. Detection of hepatitis B surface antigen and anti-hepatitis C antibodies was done using the chemiluminescence technique. To confirm chronic HCV and HBV infection in individuals with positive antibody tests, a qualitative nucleic acid test was employed as the initial diagnosis of a suspected acute infection. Ultrasound was done to complement the diagnosis of hepatitis. The data were entered in MS Excel and analysis was done by using Statistical Package for Social Sciences (SPSS) version 23.0 (IBM Corp., Armonk, NY). Shapiro-Wilk test was performed for normality and data were found normally distributed. Mean and standard deviations were computed for quantitative variables and percentages and frequencies were reported for qualitative variables. T-test was used to observe the mean difference between the two groups and a p-value <0.05 was found to be significant statistically.

A total of 351 patients were enrolled, out of which 222 (63%) were males, 265 (76%) were unmarried, 11 (3.1%)had hypertension, and 9 (2.5%) had diabetes. The mean age of participants was 30.9 27.5. Twenty-nine (8.2%) patients with AA had hepatitis. The most common hepatitis was hepatitis A, 14 (4.0%), followed by hepatitis C, 13 (3.7%). The most common form of hepatitis C was acute 9 (69.2%). Two patients had compensated cirrhosis and two patients had decompensated cirrhosis (Table 1).

The association of CBC parameters such as hemoglobin, red blood cell count, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, total leukocyte count, neutrophils, lymphocytes, monocytes, and platelets with the patients with and without hepatitis was assessed and it was found out that platelet counts were statistically significant (p-value: 0.0020) as shown in Table 2.

Table 3 depicts the association of liver profile such as serum glutamate pyruvate transaminase, gamma glutamyl transferase (GGT), serum glutamic oxaloacetic acid transaminase, PT, APTT, and international normalized ratio with the patients with and without hepatitis, and it was found out that PT (p-value< 0.0001) was statistically significant.

In our study, 8.2% of AA patients had hepatitis. This is comparatively high as compared to theprevalence of hepatitis in the general population in Pakistan, which is reported to be around 4% [20]. A retrospective study carried out in Europe from 1997 to 2007 demonstrated that HAAA patients had a slight male predominance with a value of 68% [21], which is close to the prevalence of male participants in our study, i.e. 63.2%. This European study also demonstrated that there was no causative virus for hepatitis in 94% of HAAA patients. However, 15 patients (6%) had hepatitis with nine having hepatitis B virus and six having hepatitis A virus [21]. Similar results have been observed in our study with 91.4% HAAA serologically negative and not having any signs or symptoms of hepatitis. Twenty-nine patients (8.3%) had evidence of hepatitis: hepatitis A virus in 14 patients, hepatitis B virus in 2, and hepatitis C virus in 13 patients. Assessing the association of hepatitis C virus with HAAA, a study conducted in France showed that 15.8% of HAAA patients had hepatitis C virus [22], which was approximately three-fold higher compared to our study suggesting a prevalence of 3.7% of HAAA patients with hepatitis C virus. On the contrary, slightly similar figures were recreated in another comparative study done in Thailand which showed that 5.7% of the patients who were never transfusedwere found to have hepatitis C virus [23].

During the initial course of hepatitis, cytotoxic T lymphocytes (CTLs) occupy the same receptor antigen between liver and bone marrow cells. These CTLs replicate and extend to destroy bone marrow hematopoietic stem cells and result in AA [24,25].However, another interesting finding of our study was that AA patients with hepatitis had considerably high platelet counts compared to those without hepatitis (29 28 vs 4 3). This finding is also in concordance with a study conducted by Wang WH et al. [3] in which the HAAA group had a considerably higher platelet count compared to the non-hepatitis-associated AA (50 109/L vs 12 109/L).

Literature reveals that amongthe most frequently assessed values in HAAA, there is a significant rise in ALT, GGT, and serum alkaline phosphatase [26]. The elevated levels are also shown in our results (Table 3). Considerable discrepancies were observed in PT in AA patients with and without hepatitis. This could be on account of viral hepatitis causing deranged LFTs [27].However, studies comparing the levels of liver enzymes between hepatitis-associated and non-hepatitis-associated AA are not extensively reported in the literature.

To the best of our knowledge, this is the first study at the national level to determine the association of hepatitis in patients with AA. However, the limitations of our study were that it was of cross-sectional nature and included non-probability sampling. Prospective cohort studies with stringent inclusion and exclusion criteria, a large sample size, and a controlled environment are needed to validate the findings.

AA is a heterogeneous disease with a limited approach to curative treatment options like allogeneic stem cell transplant in our region. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients should be screened for viral hepatitis at the time of diagnosis. Moreover, other causes of hepatitis should also be screened at the time of diagnosis such as parvovirus B19, human herpes virus 16, and adenovirus. Based on the rapidly advancing research methodologies, it is necessary to comprehensively analyze the underlying mechanisms of HAAA.

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Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan - Cureus

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Epidemiology of early infections and predictors of mortality after autologous hematopoietic stem-cell transplantation among multiple myeloma, Hodgkin,...

Bone Marrow Stem Cells Comments Off on Epidemiology of early infections and predictors of mortality after autologous hematopoietic stem-cell transplantation among multiple myeloma, Hodgkin,… | September 11th, 2022

September is observed as Blood Cancer Awareness month all over the world. During this month, activists and stakeholders work to raise awareness about the disease and the efforts being taken to fight blood cancers including leukemia, lymphoma, myeloma and Hodgkins disease.

The term blood cancer is a general description of various hematopoietic cancers. Our blood flows through blood vessels to supply all tissues in the body with nutrients. In the approximately 5 litres of blood circulating in our body there are billions of blood cells that carry out various vital functions. All blood cells originate from hematopoietic stem cells.

Haematopoietic stem cells are known as mother cells and do not yet have a specific function. They are able to renew and differentiate into cells with a specific function, thus replacing cells that die. In bone marrow, blood stem cells divide and develop into progenitor cells. Through further division, the progenitor cells mature and transform into different types of blood cells and then enter the bloodstream, says Dr Nitin Agarwal, HOD, Donor Request Management, DKMS BMST Foundation India.

Blood cancer is an abnormal proliferation (abnormal growth) of cells in the bone marrow especially white blood cells (WBCs). Cancer cells flood the bloodstream and drive out healthy cells. As a result, the blood can no longer perform its basic tasks, such as transporting oxygen and protecting the body from infection.

LeukemiaThis cancer is found in the bone marrow and the bloodstream. It is caused by abnormal rapid production of WBCs and high number of abnormal WBCs which cannot fight against infection, and they impair the bone marrows ability to produce red blood cells and platelets, says Dr Jimmy Mirani, Consultant Onco Surgeon, Wockhardt Hospital, Mumbai Central.

LymphomaA type of blood cancer which affects the lymphatic system, which removes the risk excess fluids from body and generates immune cells. Lymphocytes are blood cells which are used to fight against infections. These abnormal lymphocytes become lymphoma cells which multiply and get collected in the tissues, adds Dr Mirani.

There are two types of lymphoma, namely, Hodgkins lymphoma and non-Hodgkins lymphoma.

Non-Hodgkins lymphoma:It mainly impacts the B-cell or T-cell. This type of lymphoma occurs more commonly than Hodgkins lymphoma. Can vary clinically and diagnostically into slow-growing ones to very aggressive types, notes Dr. Amrita Chakrabarti, Consultant, Haemato-Oncology & Bone Marrow Transplant, Max Hospital, Shalimar Bagh.

Hodgkins lymphoma This type of lymphoma affects the B cells. Broadly divided into classical Hodgkins and nodular lymphocyte predominant types. Occurs in the adolescence or elderly age group.

MyelomaIt is the cancer of plasma cells; WBCs which produce disease and infection fighting anti-bodies. Myeloma cells prevent the functions and productions of these antibodies leaving a week immune system.

Multiple myelomaThis starts in the bone marrow when plasma cells begin to grow uncontrollably. As the cells grow, they compromise the immune system and impair the production and function of white and red blood cells causing bone disease, organ damage and anemia among other conditions, adds Dr Agarwal.

In most cases of blood cancer, the patient feels tired and weak. This happens because the number of red blood cells in the blood starts decreasing due to which there is a lack of blood in the person. Someof the commonsymptoms of blood cancers are fever, severe fatigue, bleeding from gums or skin, back ache, or bone pains, says Dr Pravas Mishra, Head Haematology/ Medical Oncology and BMT, Amrita Hospital, Faridabad.

Patients with myeloma might first present to an orthopaedical with a fracture originating from trivial trauma or to a nephrologist with a kidney dysfunction.Pain in bones and joints can be a symptom of not only arthritis but also blood cancer. Blood cancer is a disease in the bone marrow that is found in large amounts around the bones and joints.

Patientsmight present with nodes in the neck or axilla or groin or swelling in any part of the body. However most often a patientwith blood cancermight present with just a low haemoglobin. It is strongly advised not to ignore any anaemia, warns Dr Mishra.

A person suffering from blood cancer is prone to repeated infections. When leukemia cells develop in the body, then complaints of infection can be seen in the patients mouth, throat, skin, lungs, etc.

People who have cancer tend to have an abnormally low weight. If the body weight is reduced without any obvious cause, then it can be seen as the primary symptom of cancer.

The abnormal formation of leukemia cells in the body prevents the bone marrow from forming healthy blood cells such as platelets. Due to its deficiency, more bleeding problems can be seen from the nose of the patient, during menstruation and gums.

Blood cancer is diagnosed with the help of a wide range of diagnostic methods along clinical evaluation, such as blood tests, bone marrow tests, cytogenetic/karyotyping and molecular analysis, flow cytometry.

Myth: Blood cancer cannot be treated?

Fact: Once a patient is diagnosed with blood cancer, the first concern that comes to ones mind Is blood cancer curable?

Blood cancer is one type of cancer that has a high curability rate especially due to the advancement in the medical field, availability of newer, improved chemotherapy regimens, targeted therapy, and improved infection control measures. Timely diagnosis, especially early diagnosis, increases the chances of cure from blood cancer.Some of the other factors that impact the cure of blood cancer include the age of the patient, physical condition, presence of other comorbidities, stage of the disease, subtype of cancer, molecular factors, whether low grade/high grade, acute or chronic, the body parts that are affected and whether the disease is new onset or has come back after a previous cure.

You must understand that the cure or recovery from cancer is unpredictable, adds Dr. Chakrabarti.

There are cases when the patient has recovered even in the later stages of blood cancer. On the other hand, there are recorded cases where the patient couldnt recover even in the initial stages of blood cancer. So, its important to have realistic expectations and focus on following a healthy lifestyle with the advised treatment and measures. Early diagnosis and treatment play an important role in attaining cure.

Myth: All blood cancer patients need a bone marrow transplant

Fact: No, majority of patients suffering from blood cancers are treated without bone marrow transplant. A combination of chemotherapy, targeted therapy and immunotherapy is the best line of treatment.

Myth: Blood cancer occurs only in children?

Fact: No, blood cancers can occur in all age groups. All have a higher incidence in young children whereas Myeloid Leukaemia (MLL) is more frequently seen in senior citizens.

India is reeling under pressure of many misconceptions that exist amongst people about blood stem cell donation, its process and even its after-effects.

Myth: Once you donate blood stem cells, you will lose them forever.

Fact: Only a fraction of total stem cells is extracted during the process. Also, all the cells are naturally replenished within a few weeks

Myth: Donating stem cells is a really invasive and painful process

Fact: Blood stem cells are collected through peripheral blood stem cell collection (PBSC) which is completely safe and a non-surgical procedure. The process is similar to blood platelet donation that takes approximately three to four hours to complete and the donor can leave the collection center the same day.

Myth: Blood donation and a blood stem cell donation are same

Fact: Unlike blood collection for transfusion, blood stem cells are collected only when there is a match between the donor and patients human leukocyte antigen (HLA) combination (tissue type). So, you could be potentially the only match and life saver for a person with blood cancer in need of a transplant, adds Dr Nitin Agarwal. Blood stem cell donors donate only blood stem cells and the process is similar to a platelet donation.

Myth: Pregnant women cant register

Fact: This is untrue, a woman can register even during her pregnancy.

Myth: Stem cell donation leaves prolonged side-effects

Fact: No, there are no major side effects post blood stem cell donation. A person may only experience minor flu like symptoms because of the GCSF injections given to him/her before the donation, to mobilize blood stem cells in your blood stream.

Myth: Piercing and/or tattoo is a restricting factor

Fact: Piercing or a tattoo doesnt stop you from registering yourself to be a potential donor.

Myth: My blood stem cells can be stored

Fact: Your blood stem cells will not be stored. They last for around 72 hours and are delivered for the recipient straight to the hospital by a special courier. If the recipients body accepts them, the stem cells will start making healthy blood cells.

Myth: Joining a blood stem cell registry is no use. Most patients can find a stem cell donor within their own families

Fact: Per statistics, only 30% of blood disorder patients in need of a stem cell transplant are able to find a sibling match. About 70% of patients need an unrelated donor.

A registry like DKMS BMST Foundation India is a data bank of potential blood stem cell donors that houses details on thousands of committed blood stem cell donors. Any patient can benefit from this registry provided an HLA match.

Some of the blood cancer treatments include the following

Chemotherapy

This is the most important aspect of blood cancer treatment and involves using certain chemicals to kill the cancer-causing cells in the patients body. The prescribed drugs are given in a particular timeframe for the best possible improvement in the patients health. In some patients, a stem cell transplant is provided along with high dose chemotherapy.

Radiation therapyRadiation therapy helps to destroy cancer cells with the help of specific high-energy beams to kill cancer cells in precise areas of the body. This treatment is much beneficial for patients with lymphoma

Bone marrow transplantIn this procedure, healthy stem cells are utilized to replace the cells affected by cancer. This helps the patients recover in the best possible manner. Can be autologous (where stem cells are taken from the patients own body) or allogenic (when a healthy donor gives stem cells to the patient.)

Targeted Therapy

Usually in the form of oral medications or pills. They are given alongside chemotherapy/ or radiotherapy and affect specific cancer cells and help in destroying them.

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Brave Aubrey Austin, four, donated her own stem cells and saved her baby brother Carey's life on the day he turned one, after he was diagnosed with a rare type of blood cancer aged just eight months

Image: Supplied via Lucy Laing)

A brave little girl saved the life of her baby brother on his first birthday.

Carey Austin was diagnosed with a rare type of blood cancer when he was just eight months old.

His only hope of survival was a stem-cell transplant.

Against all odds, his sister Aubrey, four, was a perfect match.

Surgeons operated on Careys first birthday and six months later he is cancer-free thanks to his big sister.

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Their mum Naomi said: She absolutely adores Carey and when we explained to her about the transplant she wanted to do everything she could to save him.

Shes only four years old, yet she was only thinking of how she could help him. We felt so guilty putting her through an operation too, but it was Careys only chance of survival.

"She was so brave about it. She knew that her blood was going to save him.

During a two-hour procedure at Great Ormond Street Hospital, London, surgeons took out Aubreys stem cells and they were put into Careys body via a drip.

Naomi said: The fact that the transplant took place on Careys birthday was so significant that she was giving him a second chance at life on that special day.

The doctors and nurses said they had never seen anyone have a stem cell transplant on their birthday before.

Aubrey was very groggy and woozy when she came around from the operation, and she had puncture wounds on her back from where the stem cells had been taken out.

But she was still smiling through it all. She was so brave. She never complained about being in pain and she was just pleased to see how her little brother was afterwards.

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When the brother and sister saw each other for the first time after the operation, there was not a dry eye in the room.

Naomi said: It was so sweet when they were reunited.

We took Aubrey to see Carey and she gave him a cuddle. They were thrilled to see each other again.

After a two-day hospital stay for Aubrey and seven weeks for Carey, the family were able to settle back into life back home in Brighton, East Sussex.

Carey is now in remission, with no signs of the cancer cells in his body.

But his parents have been warned that the disease is so aggressive that until March next year there is a 40% chance of it returning. After that, the likelihood falls to just 5%.

Naomi added: Two other children lost their lives on the cancer ward while we were there, so we know how lucky Carey has been.

He and Aubrey have always been close but now their bond is stronger than ever.

"Shes a superstar and he couldnt have wanted anything more from a big sister. Hes doing so well now. He loves playing with his cars and hes just learning to walk too.

Aubrey is with him all the time she just adores him. She knows that she has saved his life and she loves being a big sister to him. They play cars together and hes learning to walk, so she stands with him encouraging him to take his steps.

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Carey fell ill last November but Naomi, a paediatric audiologist, and her husband Simon, a CPS lawyer, both 43, thought it was bronchitis because his sister had recently had the same thing.

A GP agreed but two days later he was rushed to hospital by ambulance with breathing difficulties.

Doctors at Great Ormond Street diagnosed juvenile myelomonocytic leukaemia, or JMML, which cannot be treated with chemotherapy. There are only 1.2 cases per million children in the UK each year.

Naomi said: I was hysterical. I kept trying to tell them that it wasnt cancer, it was bronchilitis. I couldnt accept what was happening.

Because parents are not suitable donors, Aubreys bone marrow was tested, a process that involves drawing a sample out using a needle.

Naomi said: There is only a 25% chance of any sibling being a match, so even with Aubrey we knew that the odds werent in our favour.

"If she hadnt been a match then we would have had to wait until doctors found an anonymous donor, but that may not have happened in time for Carey.

When the results came back to say that she was a perfect match for him, we couldnt believe it. We had been praying that she would save him, so to get the news that she was a match for him was just incredible.

When we heard I couldnt stop crying, it was so emotional. To think that Carey was going to have a chance of survival thanks to his big sister was the answer to our prayers.

The mum added: We did feel guilty about putting her through the procedure, but when we spoke to her about it, all she wanted to do was help. We were so proud of her.

The transplant was made even more special as it took place on March 15, which was Careys first birthday, giving the family a double celebration.

They are keen to raise awareness of the cancer symptoms and the charity Childhood Cancer and Leukaemia Group, which has helped them throughout their ordeal.

Naomi said: Having a child with cancer is one of the worst things that can happen to you. We didnt realise that it was leukaemia so we are thankful that it was spotted in time.

We received amazing support throughout from the hospital and from the CCLG.

We feel so lucky that Carey has come through it and it feels like a miracle to have him with us now.

Geoff Shenton, a childrens cancer specialist at Newcastle Upon Tyne Hospitals NHS Foundation, said: In a very small proportion of cases JMML can disappear on its own, but this is rare.

Most children will need a bone-marrow or stem-cell transplant. There is still a significant chance that the disease can relapse. There may be a possibility of a second transplant if this happens, but despite our best efforts, children still die from JMML.

For more information and support visit cclg.org.uk

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This months top grants in regenerative medicine, sourced from Dimensions, includes projects on: a novel platform to enhance single cell interrogation of nervous system development, human endothelial cell regulation of ossification and the development of a dynamic double network hydrogel for generating pancreatic organoids from induced pluripotent stem cells.

This project aims to investigate a strategy, which utilizes novel spatial transcriptomics approaches, integrated multiplexed RNA/protein detection and visualization and computational algorithms to identify and map molecular markers of the preganglionic neurons in the ventral spinal cord and progenitor cell populations of the sympathetic ganglia. If successful, the approach could provide a foundation for basic research of peripheral nervous system birth defects and repair using stem cell-based therapies, as well as future studies of neuroblastoma initiation.

Funding amount:US$206,000

Funding period: 8 August 2022 31 July 2024

Funder:Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Research organization:Stowers Institute for Medical Research (MO, USA)

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Over one million patients undergo bone repair procedures in the USA annually, with autologous bone grafting remaining the preferred treatment for bone defects. The development of therapies that exploit the osteogenic potential of bone marrow-derived mesenchymal stem cells (bm-MSCs) has been limited due to limited understanding of the regulatory mechanisms of in vivo bm-MSC osteogenesis. Previous research from the group showed that the osteogenic potential of bm-MSCs is dependent on sustained proximity to endothelial cells. The goal of the present study is to elucidate the cellular and molecular mechanisms by which endothelial cells regulate the osteogenic differentiation of bm-MSCs and develop a foundation of knowledge upon which to build therapeutic strategies for bone regeneration utilizing autologous bm-MSCs.

Funding amount:US$442,000

Funding period: 10 August 2022 31 May 2027

Funder:National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Research organization:Boston Childrens Hospital (MA, USA)

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Human induced pluripotent stem cells provide a valuable source of cells for basic research and translational applications. While there have been advances in lineage-specific differentiation of human induced pluripotent stem cells, there remains limited understanding on the impact of matrix stiffness, viscoelasticity and integrin ligand presentation on the multi-stage development of exocrine pancreatic organoids. This research aims to define the influence of matrix properties on the generation of exocrine pancreatic organoids by developing a viscoelastic dynamic double network hydrogel platform with controllable matrix mechanical properties and biochemical motifs. This will advance the application of chemically defined matrices as xeno-free artificial stem cell niches for organoid growth and tissue regeneration applications.

Funding amount:US$468,000

Funding period: 1 August 2022 31 July 2026

Funder:National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Research organization: Indiana University Purdue University Indianapolis (IA, USA)

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Top 3 grants in regenerative medicine: July 2022 - RegMedNet

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Fast-track status is granted for frontotemporal dementia, next to the existing designation for traumatic spinal cord injury

GELEEN, Netherlands, Sept. 8, 2022 /PRNewswire/ -- The European Union has grantedstem cell biotech Neuroplastan orphan medicinal product designation for the applicability of its stem cell technology platform to frontotemporal dementia (FTD), following a positive opinion from The European Medicines Agency (EMA). With the existing orphan disease designation (ODD) for traumatic spinal cord injury (TSCI), Neuro-Cells is now approved for a fast-track development pathway with market exclusivity for both a trauma-induced and a chronic degenerative central nervous system disorder. This marks an important milestone in the development roadmap of Neuroplast's Neuro-Cells platform, as a stepping stone to other chronic neurodegenerative diseases such as Alzheimer's, ALS and Parkinson's Disease. The potential width in therapeutic applicability of the Neuroplast technology gives perspective to millions of people suffering from neurodegenerative diseases that currently have no outlook on effective treatment.

One technology addresses underlying mechanisms of multiple acute and chronic neurological disorders

Several conditions of the central nervous system, even when they seem unrelated at first and may have distinctive causes, have similar underlying disease mechanisms in common. These include unprogrammed cell death boosted by inflammation. Neuro-Cells, an autologous, bone-marrow derived Advanced Therapy Medicinal Product, addresses that disease mechanism by moderating inflammation of damaged cells in the central nervous system, to limit further impairment. The treatment objective in acute disorders is to limit impact of sudden injury, where the treatment objective in chronic disorders is to limit progression of the disease.

Neuroplast is already running a fast-track development pathway for traumatic spinal cord injury (TSCI), with a Phase II clinical trial in progress. This designation for frontotemporal dementia illustrates the broader applicability of the same technology for acute as well as chronic neurodegenerative disorders, paving the way to explore further applicability to conditions such as ALS, Alzheimer's disease, traumatic brain injury, subarachnoid stroke and Parkinson's Disease.

Orphan disease designation for FTD awarded based on pre-clinical evidence

Orphan disease designations are restricted to products for rare conditions for which there are no satisfactory methods of treatment authorized. It allows for a faster market authorization pathway and ten-year market exclusivity.

Frontotemporal dementia (FTD) is a degenerative condition in the brain that affect approximately 3.8 people in 10,000 persons in the EU. Typical survival rate lies between three and fourteen years from symptom onset, dependent on the FTD variant at play.

For this approval, the European Union followed the positive opinion from the EMA after the EMA followed positive recommendations from the Committee for Orphan Medicinal Products (COMP). COMP partly based their conclusions on the availability of pre-clinical evidence in mice, that showed decrease in neuroinflammation markers and rescue of cognitive and social behavioral deficits. Examples include reduction of anxiety, depressive-like behavior and abnormal social behavior.

Neuroplast CEO Johannes de Munter states:

"This designation for frontotemporal dementia is an important milestone in expanding the Neuro-Cells development to a wider range of therapeutic areas. Using the same technology platform for traumatic spinal cord injury and frontotemporal dementia, illustrates an unusual range of acute and chronic neurological disorders that could potentially benefit from this."

Neuroplast is open to discuss investor opportunities to effectuate the clinical pathways to a wider scope of neurological conditions.

About Frontotemporal dementia

Frontotemporal dementia (FTD) is a degenerative condition in the brain that is characterized by behavioral and language impairments. Depending on the variant, patients experience changes in personality, emotion, speech or motor functions. Patients may first become indifferent or careless and have difficulty understanding sentences. While the condition progresses, patients may become language impaired, lack initiative and lose executive functions. The typical survival rate lies between three and fourteen years from symptom onset, dependent on the FTD variant at play.

FTD affects approximately 3.8 people in 10,000 persons in the EU, for whom there are no effective treatments available. Patients typically receive antipsychotics to limit behavioral symptoms.

About Neuro-Cells

Neuro-Cells is a transformative treatment under GMP. It contains non-substantially manipulated bone marrow-derived hematopoietic and mesenchymal stem cells, manufactured from a patient's own bone marrow (donor and receiver are the same person). Inflammatory inducing components and pathogens are removed during this process.

About Neuroplast

Neuroplast is a Dutch stem cell technology company focusing on fast-track development programs using autologous cell products for treatment of neurodegenerative diseases, with the aim of giving back perspective to people who suffer from those conditions.

The company was founded in August 2014 by physician Johannes de Munter and neurologist Erik Wolters. Current funders are Lumana Invest, Brightlands Venture Partners, LIOF and the Netherlands Enterprise Agency. Neuroplast is located at Brightlands Chemelot Campus in The Netherlands.

For more information, please visite http://www.neuroplast.com

About Lumana Invest

Investment company Lumana was established by entrepreneurs and unique due to not having a predetermined investment horizon. The Lumana founders showcase strong commitment to their portfolio companies by actively supporting management in strategic decision making.

About Brightlands Venture Partners

Brightlands Venture Partners (BVP) is the fund manager of Chemelot Ventures and is a so-called ecosystem investor. BVP invests in companies benefiting from and contributing to the Brightlands campuses in the south of The Netherlands. Other funds under management are BVP Fund IV, Brightlands Agrifood Fund and Limburg Ventures. The funds of BVP focus on sustainability and health; together the funds have made over 40 investments.

About LIOF

LIOF is the regional development agency for Limburg and supports innovative entrepreneurs with advice, network and financing. Together with entrepreneurs and partners, LIOF is working towards a smarter, more sustainable and healthier Limburg by focusing on the transitions of energy, circularity, health and digitalization.

About The Netherlands Enterprise Agency

The Netherlands Enterprise Agency operates under the auspices of the Dutch Ministry of Economic Affairs and Climate Policy. It facilitates entrepreneurship, improves collaborations, strengthens positions and helps realize national and international ambitions with funding, networking, know-how and compliance with laws and regulations.

Forward looking statements

All statements other than statements of historical facts, including the statements about the clinical and therapeutic potential and future clinical milestones of Neuro-Cells, the indications we intend to pursue and our possible clinical or other business strategies, and the timing of these events, are forward-looking statements. Forward-looking statements can be identified by terms such as "believes", "expects", "plans", "potential", "would" or similar expressions and the negative of those terms. These forward-looking statements are based on our management's current beliefs and assumptions about future events and on information currently available to management. Neuroplast B.V. does not make any representation or warranty, express or implied, as to the improper use of this article, accuracy, completeness or updated status of above-mentioned statements. Therefore, in no case whatsoever will Neuroplast B.V. be legally liable or liable to anyone for any decision made or action taken in conjunction with the information and/or statements in this press release or for any related damages.

In case of any further questions, please contact:

Neuroplast

Johannes de Munter, CEOT: +31 (0)85 076 1000E: [emailprotected]

LifeSpring LifeSciences Communication, Amsterdam

Leon MelensT: +31 6 538 16 427E: [emailprotected]

Logo: https://mma.prnewswire.com/media/1666795/Neuroplast_Logo.jpg

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Neuroplast receives second orphan medicinal product designation for Neuro-Cells, paving the way for application to both chronic and trauma-induced...

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How do bone marrow transplants work, and what conditions do they treat?

A bone marrow transplant is actually a misnomer, as these procedures transplant stem cells, not the actual bones. Specifically, these procedures use hematopoietic stem cells (HSC), also known as blood-forming stem cells, to potentially cure an ever-expanding number of diseases.

There are three main cell types found inside a persons blood based on their function:

red blood cells: these cells carry oxygen throughout the body

platelets: these cells help form clots to stop bleeding

white blood cells: these cells lead the charge in fighting infections (also known as the immune system)

Each of these cell types, despite their different functions, shapes, sizes and lifespan, arise from the same source the hematopoietic stem cell, which constantly replenish each cell type. HSCs reside almost exclusively deep inside our bones in the center of the hard, protective shelter of calcium and other minerals. So, the marrow (soft, middle portion of our bones) can be thought of as the factory that supply each person with the blood cells needed to overcome infections, trauma, and to live a healthy, long life.

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When we perform a transplant, we are actually either using a patients own stem cells (autologous transplant) or stem cells from another human (allogeneic transplant), leading to the more appropriate name of hematopoietic stem cell transplant (HSCT). These transplants are most commonly used to treat and cure cancer.

Autologous transplants are used in the treatment of many types of solid tumors (such as brain tumors, germ cell tumors, neuroblastoma), where the tumor can only be effectively destroyed by giving very high doses of chemotherapy that also damage the patients own HSCs. Before giving a patient those high doses of chemotherapy, we collect his or her own HSCs with a process very similar to dialysis (we remove stem cells from their blood), and then freeze and store them in a specialized lab.

After the patient receives that high dose of chemotherapy, the treatment team then thaws the stem cells and infuses them back into the patient via a specialized catheter placed in his or her veins. The stem cells quickly return home and find the bone marrow space, and within 10 to 21 days, they will start making new white blood cells and platelets, followed by red blood cells.

Allogeneic transplants are performed for many types of leukemias or bone marrow failure syndromes (such as aplastic anemia or Fanconi anemia) where the patients own stem cells are broken and need to be replaced by a healthy humans stem cells. However, many other non-malignant conditions (not cancer) can be effectively cured with this procedure, as conditions that result from defects of different blood cell types (red blood cells, white blood cells or platelets) are corrected when the factory is replaced with a healthy donors stem cells.

This is an exciting time in the field of transplant, as we are now able to offer cures for many childhood diseases that historically are chronic and/or life-threatening. HSCT is now being offered to patients with sickle cell disease/thalassemia (red blood cells are defective), along with many conditions that are now called inborn errors of immunity (white blood cells are defective).

Among the more than 500 different genetic conditions that damage white blood cells include severe combined immunodeficiency (SCID), hemophagocytic lymphohistiocytosis (HLH), chronic granulomatous disease (CGD), and severe congenital neutropenia (SCN). Not only are the numbers of conditions potentially cured with HSCT rapidly growing, but the success rates and ability to prevent and treat complications of this procedure are improving exponentially as well. We are looking forward to offering these procedures to more children here at UVa Childrens.

To learn more about Dr. Roehrs and the care he provides, visit uvahealth.com/findadoctor/profile/philip-a-roehrs.

Dr. Philip Roehrs is the clinical director for pediatric stem cell transplant and cellular therapy at UVa Childrens and UVa Health.

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Ask the Expert: How do bone marrow transplants work, and what conditions do they treat? - The Daily Progress

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City of Hope recently shared significant news at the 24th Annual AIDS Conference about a patient treated in 2019 whose HIV has been in remission. The man had been living with HIV for 31 years before coming to City of Hope with another grave diagnosisacute myeloid leukemia.One of the best hopes for long-term remission of acute myeloid leukemia (AML) is a stem cell transplant, and City of Hope has one of the nations leading transplant programs, having performed more than 17,000 transplants since 1976. In addition, the institution is at the forefront of using transplants to treat older adults with blood cancers, including increasing efficacy and safety in those over 60 and those with comorbidities, like the then 63-year-old City of Hope patient with HIV. The research was presented by Jana K. Dickter, M.D., City of Hope associate clinical professor in the Division of Infectious Diseases.

City of Hope hematologist Ahmed Aribi, M.D., assistant professor in the Division of Leukemia, prepared the patient for an allogeneic blood stem cell transplant with a chemotherapy-based, reduced-intensity regimen developed for treatment of older patients with blood cancers. Reduced-intensity chemotherapy makes the transplant more tolerable for older patients and reduces the potential for transplant-related complications from the procedure.

Aribi and his team worked with City of Hopes Unrelated Donor BMT Program directed by Monzr M. Al Malki, M.D. to find a donor who was a perfect match for the patient and had the rare genetic mutation, homozygous CCR5 Delta 32, which is found in just 1 to 2% of the general population.

People who have this mutation have a resistance to acquiring HIV. CCR5 is a receptor on CD4+ immune cells, and most strains of HIV use that receptor to enter and attack the immune system. But the CCR5 mutation blocks that pathway, which stops HIV from replicating.

After this successful transplant for both AML and HIV, the patient has been in remission for HIV since stopping ART in March 2021. While this outcome has happened in three other patients, the City of Hope patient was both the oldest to undergo a transplant with HIV and leukemia and go into remission for both. He had also lived with HIV the longest 31 years.

The City of Hope patient is another major advancement. It demonstrates that research and clinical care developed and led at City of Hope are changing the meaning of an HIV diagnosis for patients across the United States and the world, said John Zaia, M.D., director of City of Hopes Center for Gene Therapy, Aaron D. Miller and Edith Miller Chair for Gene Therapy and a leader in HIV research. City of Hope remains at the forefront of clinical research that changes peoples lives for the better.

When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence. I never thought I would live to see the day that I no longer have HIV. City of Hope made that possible, and I am beyond grateful. The City of Hope patient

The story above is one significant example of several important advances being made at City of Hope in the care of people with HIV. When many centers still treated patients with low-intensity, noncurative treatment approaches for HIV-related lymphoma, City of Hope challenged that paradigm by demonstrating that autologous transplantation could be used to cure patients who would otherwise die.

More recently, City of Hope is leveraging its leadership in CAR T cell therapya groundbreaking treatment currently used to rally the bodys natural defenses against cancer and exploring its potential in tandem with another advance, City of Hopes vaccine for cytomegalovirus (CMV).

In a proof-of-concept study, funded by theCalifornia Institute for Regenerative Medicine, lab models demonstrated that the combination therapy could recognize and eliminate HIV without serious toxicity to cells in the virus host. In cultured human cells, the CAR T cells killed cells tagged with the gp120 protein, and kept killing them, without significant signs of risking damage to healthy cells. In a mouse model for HIV/AIDS, high doses of the dual-action CAR T cells followed by the CMV vaccine were successful in controlling HIV, and even nestled into the bone marrow, indicating potential for treatment to keep working over the long term.

In addition to achieving breakthrough outcomes in cancer and HIV, City of Hope has been recognized as the seventh "Best Hospital" for cancer in the nation according to U.S. News & World Report's 2022-23 Best Hospitals: Specialty Ranking. This marks the first time the cancer treatment center has cracked the top 10 of the U.S. News & World Report annual rankings and the 16th consecutive year it has been distinguished as one of the nation's elite cancer hospitals. It was also rated as high performing in four cancer surgery specialties: lung, colon, prostate and ovarian cancers.

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From optimized stem cell transplants to CAR T cell therapy: Advancing options for cancer, HIV and more - City of Hope

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So far, Bcells havent gotten the same attentionindeed, genetically engineered versions have never been tested in a human. Thats partly because engineering B cells is not that easy, says Xin Luo, a professor at Virginia Tech who in 2009 demonstrated how to generate B cells that have an added gene.

That early work, carried out at Caltech, explored whether the cells could be directed to make antibodies against HIV, perhaps becoming a new form of vaccination.

While that idea didnt pan out, now biotech companies like Immusoft, Be Biopharma, and Walking Fish Therapeutics want to harness the cells as molecular factories to treat serious rare diseases. These cells are powerhouses for secreting protein, so thats something they want to take advantage of, says Luo.

Immusoft licensed the Caltech technology and got an early investment from Peter Thiels biotech fund, Breakout Labs. Company founder Matthew Scholz, a software developer, boldly predicted in 2015 that a trial could start immediately. However, the technology the company terms immune-system programming didnt turn out to be as straightforward as coding a computer.

Ainsworth says Immusoft had to first spend several years working out reliable ways to add genes to B cells. Instead of using viruses or gene editing to make genetic changes, the company now employs a transposona molecule that likes to cut and paste DNA segments.

It also took time to convince the FDA to allow the trial. Thats because its known that if added DNA ends up near cancer-promoting genes, it can sometimes turn them on.

The FDA is concerned if you are doing this in a B cell, could you develop a leukemia situation? That is something that they are going to watch pretty closely, says Paul Orchard, the doctor at the University of Minnesota who will be recruiting patients and carrying out the study.

The first human test could resolve some open questions about the technology. One is whether the enhanced cells will take up long-term residence inside peoples bone marrow, where B cells typically live. In theory, the cells could survive decadeseven the entire life of the patient. Another question is whether theyll make enough of the missing enzyme to help stall MPS, which is a progressive disease.

Continued here:
A new gene therapy based on antibody cells is about to be tested in humans - MIT Technology Review

Bone Marrow Stem Cells Comments Off on A new gene therapy based on antibody cells is about to be tested in humans – MIT Technology Review | September 3rd, 2022

North America Market Comprises Of 53.1% Market Share Due To Rising Number Of Spine-Related Disorders

Fact.MR A Market Research and Competitive Intelligence Provider: Theglobal bone grafts and substitutes marketreached a valuation ofUS$ 3.06 Bnin 2020. Moreover, sales of bone grafts and substitutes are slated to rise at a CAGR of4.9%to reachUS$ 4.44 Bnby the end of 2028.

Bone grafts and substitutes (BGS) are rapidly used common materials used mainly to replace missing bones or mend fractures. Moreover, it is commonly being used in the hip, foot, and ankle surgeries, as well as fractures and musculoskeletal injuries. Moreover, the primary goal of using bone grafts and substitutes is to aid in the healing of fractures and bone injuries, as well as to replace natural bone.

Moreover, surge in demand for synthetics and xenografts, rise in usage of bone graft substitutes in regenerative medicines, and the surge in the number of illnesses that necessitate their usage would propel the market for bone grafts and substitutes forward.

In addition to this, continuous R&D initiatives to upgrade product offerings are one of the most common trends in the market. This rise in R&D initiatives is driven by surge in need for bone graft substitutes for bone-related occurrences fractures and trauma. Researchers from across the globe are putting in efforts to find new ways to use bone grafts in regenerative medicines.

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Bone grafts manufacturers are constantly investing in the development of new products with improved bioactivity, biocompatibility, and mechanical qualities. Companies have a varied product portfolio that is technologically advanced, as well as a larger global presence. Key players in the market are putting emphasis on innovative products in various orthopedic application areas.

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Bone Grafts And Substitutes Market Is Expected To Witness An Impressive CAGR Of 4.9% Due To Rise In Usage Of Bone Grafts And Substitutes For Healing...

Bone Marrow Stem Cells Comments Off on Bone Grafts And Substitutes Market Is Expected To Witness An Impressive CAGR Of 4.9% Due To Rise In Usage Of Bone Grafts And Substitutes For Healing… | September 3rd, 2022

By Giles Campion, EVP, head of R&D and chief medical officer, Silence Therapeutics

siRNA is a gene-silencing technology with great potential for treating a wide range of rare diseases, as I discussed in my previous article, but its promise doesnt end there. In this last article in the series, I examine siRNAs potential for treating not-so-rare and even quite common diseases.

Unlike rare diseases, which are often caused by pathological genetic mutations, common diseases may be associated with genetic variants that are not pathological and therefore do not dysregulate a biological process. For example, variants of the LPA or PCSK9 gene can increase a persons risk of cardiovascular disease by affecting cholesterol levels, but these variants do not directly cause cardiovascular disease by disrupting a fundamental biological process. This contrasts with, for example, mutations in the HBB gene that cause beta thalassemia and disrupt the mechanisms that protect the body from toxic iron buildup.

Nevertheless, the approach to treating rare and common diseases with siRNA therapies is similar: silence a gene that has little or no effect on phenotypes outside the disease, thereby maximizing safety. This is an important factor in rare diseases, which often begin early in life and require lifelong treatment. But it is equally important in common chronic diseases, such as hyperlipidemia, in which a patient has abnormally high levels of fats in the blood, where patients may live for decades before they experience any overt symptoms from their condition and are not likely to tolerate a therapy with even minor side effects that interfere with their quality of life.

At the forefront of common conditions being targeted by gene silencing is elevated lipoprotein (a), or Lp(a), a cholesterol-rich particle closely related to the well-known cardiovascular risk factor LDL. High levels of Lp(a) are associated with high risk of cardiovascular events, such as heart attacks and strokes; low levels of Lp(a) are associated with a low risk of these events.

Unlike other types of cholesterol-carrying particles, Lp(a) levels are not significantly modifiable by lifestyle factors; levels are genetically determined by the variant of the LPA gene, which encodes apolipoprotein (a) a major protein component of Lp(a) that a person has. Because these variants are not pathological mutations, the person may not experience disease symptoms for years and may even be unaware of their elevated Lp(a) levels. Yet the condition is common: One in five people have high levels of Lp(a), defined as 50 mg/dl or 120 nmol/L. Other cholesterol-reducing medicines, such as statins, have no effect on Lp(a) and can even increase levels; currently there are no approved Lp(a)-reducing therapies.

However, assessments of human genetic databases, such as the UK Biobank, have revealed that cardiovascular risk is the only phenotype associated with Lp(a) levels. Some individuals have zero levels of Lp(a), and the only known phenotype in them is a much-reduced incidence of cardiovascular events. This indicates that silencing LPA with a properly designed siRNA therapy, such as Silences clinical-stage asset SLN360, could reduce the risk of cardiovascular disease in people with elevated Lp(a) while minimizing the risk of any unwanted or unexpected side effects.

The PCSK9 gene is another example of an siRNA target for the common condition of hyperlipidemia. The PCSK9 protein negatively regulates the cellular uptake of low-density lipoprotein-cholesterol (LDL-C) in the bloodstream by reducing the number of LDL receptors on the surface of cells. This means that high levels of PCSK9 decrease cellular uptake of LDL-C, leaving more of it in circulation.

High LDL-C levels in blood are associated with coronary artery disease (CAD). While not entirely determined by genetics, as Lp(a) levels are, some variants of the PCSK9 gene are associated with low levels of LDL-C and a reduced incidence of cardiovascular disease. Similar to the LPA gene, this suggests that silencing PCSK9 with an siRNA could reduce LDL-C levels in the blood to treat hyperlipidemia and reduce the risk of CAD. Indeed, the siRNA therapy inclisiran, which silences PCSK9, was approved by the European Union in December 2020 and in the United States in December 2021 for use in people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk equivalents, and heterozygous familial hypercholesterolemia (HeFH), in conjunction with lifestyle changes and other cholesterol-lowering medicines.

An important feature of siRNA therapies in the treatment of common chronic conditions such as elevated Lp(a) and elevated LDL-C is that they have long-lasting effects, and thus they require less frequent dosing than statins and other small molecule drugs, which must be taken daily. This in turn should increase patients compliance with the therapeutic regimen and thereby improve outcomes. In fact, a 2018 retrospective study found that hyperlipidemia patients who were prescribed the right intensity (level) of statin treatment and complied 100% with their therapy had a 40% lower risk of cardiovascular events than patients who received low-intensity statin treatment and had 5% compliance.1The study concluded that an optimal therapy could reduce the risk of cardiovascular events by 30% in three years.

Though published before any siRNA therapy was approved for hyperlipidemia, the studys implications are clear: Therapeutic intensity and patient compliance are important factors in saving peoples lives. With siRNA therapies, the intensity is known, and the compliance issues are likely to be less of an issue compared with oral drugs. This is just one aspect of siRNA that makes it as well-suited for treating common diseases as rare diseases.

siRNA also has the potential to improve outcomes in hematopoietic stem cell transplantation (HSCT). Though not a disease per se, HCST is a procedure commonly used to treat a range of blood cancers and, with increasing frequency, certain autoimmune disorders.

HCST involves ablating the existing bone marrow to make way for a healthy stem cell graft to repopulate the marrow. This ablation shifts an enormous load of dead iron-laden blood cells into the circulation. Retrospective studies suggest this acute release of toxic iron from ablated cells can adversely affect the survival of the stem cell graft and increase the risk of potentially lethal infections in HSCT patients.

As in the rare disease examples I mentioned previously, silencing TMPRSS6 with an siRNA could increase hepcidin to reduce iron levels in HSCT patients, potentially improving their survival and engraftment outcomes.

I am passionate about RNA technology and the benefits that targeted, precision siRNA medicines can bring to patients with rare diseases and not-so-rare diseases who need new therapeutic options. As both a physician and drug developer, I find it rewarding and exciting to witness this technology finally coming into its own, with the promise of delivering even greater benefits in the coming years.

Reference

About The Author:

Giles Campion, MD, joined Silence Therapeutics as head of R&D and chief medical officer in 2019 and was appointed as an executive director in 2020. He is an expert in translational medicine and an experienced biotech and pharmaceutical professional across many therapeutic areas, most recently in orphan neuromuscular disorders. He has held senior global R&D roles in several large pharma, diagnostics, and biotech companies, including as group vice president of the neuromuscular franchise at BioMarin Pharmaceutical Inc., and chief medical officer and senior vice president of R&D at Prosensa. He is also a co-founder of PepGen Ltd. He earned his bachelors and doctorate degrees in medicine from the University of Bristol and is listed on the General Medical Council (UK) Specialist Register (Rheumatology).

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The Promise Of Gene Silencing To Treat Not-So-Rare Diseases - BioProcess Online

Bone Marrow Stem Cells Comments Off on The Promise Of Gene Silencing To Treat Not-So-Rare Diseases – BioProcess Online | September 3rd, 2022

Figure 3. HSCs and restricted haematopoietic progenitors occupy distinct niches in the bone marrow

a. HSCs are found mainly adjacent to sinusoids throughout the bone marrow,,,, where endothelial cells and mesenchymal stromal cells promote HSC maintenance by producing SCF, CXCL12,,, and likely other factors. Similar cells may also promote HSC maintenance around other types of blood vessels, such as arterioles. The mesenchymal stromal cells can be identified based on their expression of Lepr-Cre, Prx1-Cre, Cxcl12-GFP, or Nestin-GFP transgene in mice and similar cells are likely to be identified by CD146 expression in humans. These perivascular stromal cells, which likely include Cxcl12-abundant Reticular (CAR) cells, are fated to form bone in vivo, express Mx-1-Cre and overlap with CD45/Ter119PDGFR +Sca-1+ stromal cells that are highly enriched for MSCs in culture. b. It is likely that other cells also contribute to this niche, likely including cells near bone surfaces in trabecular rich areas. Other cell types that regulate HSC niches include sympathetic nerves,, non-myelinating Schwann cells (which are also Nestin+), macrophages, osteoclasts, extracellular matrix ,, and calcium. Osteoblasts do not directly promote HSC maintenance but do promote the maintenance and perhaps the differentiation of certain lymphoid progenitors by secreting Cxcl12 and likely other factors,,,. Early lineage committed progenitors thus reside in an endosteal niche that is spatially and cellularly distinct from HSCs.

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The bone marrow niche for haematopoietic stem cells - PubMed

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What Is a Bone Marrow Transplant?

A bone marrow transplant is a medical procedure performed to replace bone marrow that has been damaged or destroyed by disease, infection, or chemotherapy. This procedure involves transplanting blood stem cells, which travel to the bone marrow where they produce new blood cells and promote growth of new marrow.

Bone marrow is the spongy, fatty tissue inside your bones. It creates the following parts of the blood:

Bone marrow also contains immature blood-forming stem cells known as hematopoietic stem cells, or HSCs. Most cells are already differentiated and can only make copies of themselves. However, these stem cells are unspecialized, meaning they have the potential to multiply through cell division and either remain stem cells or differentiate and mature into many different kinds of blood cells. The HSC found in the bone marrow will make new blood cells throughout your lifespan.

A bone marrow transplant replaces your damaged stem cells with healthy cells. This helps your body make enough white blood cells, platelets, or red blood cells to avoid infections, bleeding disorders, or anemia.

Healthy stem cells can come from a donor, or they can come from your own body. In such cases, stem cells can be harvested, or grown, before you start chemotherapy or radiation treatment. Those healthy cells are then stored and used in transplantation.

Bone marrow transplants are performed when a persons marrow isnt healthy enough to function properly. This could be due to chronic infections, disease, or cancer treatments. Some reasons for a bone marrow transplant include:

A bone marrow transplant is considered a major medical procedure and increases your risk of experiencing:

The above symptoms are typically short-lived, but a bone marrow transplant can cause complications. Your chances of developing these complications depend on several factors, including:

Complications can be mild or very serious, and they can include:

Talk to your doctor about any concerns you may have. They can help you weigh the risks and complications against the potential benefits of this procedure.

There are two major types of bone marrow transplants. The type used will depend on the reason you need a transplant.

Autologous transplants involve the use of a persons own stem cells. They typically involve harvesting your cells before beginning a damaging therapy to cells like chemotherapy or radiation. After the treatment is done, your own cells are returned to your body.

This type of transplant isnt always available. It can only be used if you have a healthy bone marrow. However, it reduces the risk of some serious complications, including GVHD.

Allogeneic transplants involve the use of cells from a donor. The donor must be a close genetic match. Often, a compatible relative is the best choice, but genetic matches can also be found from a donor registry.

Allogeneic transplants are necessary if you have a condition that has damaged your bone marrow cells. However, they have a higher risk of certain complications, such as GVHD. Youll also probably need to be put onmedications to suppress your immune system so that your body doesnt attack the new cells. This can leave you susceptible to illness.

The success of an allogeneic transplant depends on how closely the donor cells match your own.

Prior to your transplant, youll undergo several tests to discover what type of bone marrow cells you need.

You may also undergo radiation or chemotherapy to kill off all cancer cells or marrow cells before you get the new stem cells.

Bone marrow transplants take up to a week. Therefore, you must make arrangements before your first transplant session. These can include:

During treatments, your immune system will be compromised, affecting its ability to fight infections. Therefore, youll stay in a special section of the hospital thats reserved for people receiving bone marrow transplants. This reduces your risk of being exposed to anything that could cause an infection.

Dont hesitate to bring a list of questions to ask your doctor. You can write down the answers or bring a friend to listen and take notes. Its important that you feel comfortable and confident before the procedure and that all of your questions are answered thoroughly.

Some hospitals have counselors available to talk with patients. The transplant process can be emotionally taxing. Talking to a professional can help you through this process.

When your doctor thinks youre ready, youll have the transplant. The procedure is similar to a blood transfusion.

If youre having an allogeneic transplant, bone marrow cells will be harvested from your donor a day or two before your procedure. If your own cells are being used, theyll be retrieved from the stem cell bank.

Cells are collected in two ways.

During a bone marrow harvest, cells are collected from both hipbones through a needle. Youre under anesthesia for this procedure, meaning youll be asleep and free of any pain.

During leukapheresis, a donor is given five shots to help the stem cells move from the bone marrow and into the bloodstream. Blood is then drawn through an intravenous (IV) line, and a machine separates out the white blood cells that contain stem cells.

A needle called a central venous catheter, or a port, will be installed on the upper right portion of your chest. This allows the fluid containing the new stem cells to flow directly into your heart. The stem cells then disperse throughout your body. They flow through your blood and into the bone marrow. Theyll become established there and begin to grow.

The port is left in place because the bone marrow transplant is done over several sessions for a few days. Multiple sessions give the new stem cells the best chance to integrate themselves into your body. That process is known as engraftment.

Through this port, youll also receive blood transfusions, liquids, and possibly nutrients. You may need medications to fight off infections and help the new marrow grow. This depends on how well you handle the treatments.

During this time, youll be closely monitored for any complications.

The success of a bone marrow transplant is primarily dependent on how closely the donor and recipient genetically match. Sometimes, it can be very difficult to find a good match among unrelated donors.

The state of your engraftment will be regularly monitored. Its generally complete between 10 and 28 days after the initial transplant. The first sign of engraftment is a rising white blood cell count. This shows that the transplant is starting to make new blood cells.

Typical recovery time for a bone marrow transplant is about three months. However, it may take up to a year for you to recover fully. Recovery depends on numerous factors, including:

Theres a possibility that some of the symptoms you experience after the transplant will remain with you for the rest of your life.

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Bone Marrow Transplant: Types, Procedure & Risks - Healthline

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Cord blood banking can treat a wide range of illnesses. This type of blood contains high concentrations of special stem cells. The stem cells collected from the umbilical cord can assist with autoimmune disorders and other diseases. The process of cord blood banking often occurs when a medical professional such as an obstetrician-gynecologist takes blood from an umbilical cord after the birth of a baby. The cord blood is then collected and processed. Cord blood banking has the potential to save lives.

Collected cord blood treats many diseases. The diseases that cord blood is known to combat range from leukemia to sickle cell anemia. The cord blood often helps improve an individuals immune system and bone marrow. The blood thats found within the umbilical cord is considered special because it treats a wide range of illnesses. Although it tends to work best for the child and mother, the blood can also assist other people if the results from testing for matches prove beneficial. Collecting cord blood remains an excellent option for parents and people with histories of certain illnesses. Cord blood collection is recommended for people interested in taking a proactive approach to potential future illnesses. As the saying goes, health is wealth.

Collecting cord blood and cord tissue is important because the stem cells they contain can transform into other human cells. Stem cells offer flexibility and adaptability that can prove useful when treating certain cancers.

The stem cells collected from cord blood offer almost 10 times the number of stem cells that can be collected using alternative types of collection. The process of collecting stem cells from a clamped umbilical cord after birth is considered an easier process than collecting stem cells from bone marrow.

Stem cells collected from cord blood are viewed as more favorable than those collected from bone marrow because the stem cells from cord blood have a lower likelihood of passing on blood-borne illnesses.

Cord blood remains a scarce resource for both research and stem cell transplants because of a low and limited supply. The amount of cord blood that can be collected remains relatively low because only so much can be collected after birth.

The blood is drawn from a clamped umbilical cord after birth and placed into a sterile bag. Cord blood is tested before it is accepted by a cord blood bank. Not every unit of cord blood meets the specified criteria. For example, some units of cord blood are not deemed worth the resources to cryogenically save because they lack stem cells. The cord blood is examined to make sure that it is not contaminated and does not contain any potential diseases. Blood is also tested to know if it has a high-enough level of blood-forming cells. Such inspections help create safeguards for people interested in obtaining cord blood for treatment. Cord blood that does not meet the strict standards for transplant use can be used for research.

The process of collecting cord blood for public cord blood banks is often not possible with twins because they are often born much smaller than other babies in addition to often having less cord blood. Public banks typically do not allow collections from twin births. In contrast, private banks will store cord blood from twins for possible use by the family.

Private cord blood banks are an excellent option in case one of your children becomes sick. If one of your children becomes ill, then having saved their cord blood or cord tissue can boost their immune system or improve bone marrow. Having a childs previously saved cord blood from their umbilical cord improves the likelihood of a successful transplant. The blood fights certain cancers as well as specific blood disorders.

An additional benefit of cord blood banking is that other siblings and close family members can use the blood. Using the stem cells from a sibling can prove useful if one of your children develops a genetic disorder. For example, a person with a genetic disorder such as cystic fibrosis cannot be treated by their own cord blood. Cord blood collected from the siblings of that person can often be used to combat the disorder.

A public cord blood bank follows government regulations to protect the public from harm by maintaining certain set standards. The banks follow a wide range of regulations such as state laws and regulations in combination with U.S. Food and Drug Administration (FDA) regulations. If a collected unit or sample of cord blood does not meet the set standards, it is usually used for research or discarded.

Public cord blood banks allow individuals to obtain cord blood for uses such as stem cell transplants. Cord blood units collected and provided to a public cord blood bank are usually placed on a registry to more easily be matched with patients in need.

Cord blood is stored in a public or private cord blood bank with cryogenic preservation.

Some cord blood banks offer the option to preserve both cord blood and cord tissue to collect different types of cells. If possible, saving both the cord blood and cord tissue can help collect more cells for future use.

Private cord blood banks allow direct family members and approved individuals to access personally stored cord blood. In contrast, public cord blood banks collect donations of blood usually at no cost to the donor. The collections at a public bank are then accessible to members of the public on an as-needed basis for allogeneic transplants.

Private cord blood banks: Private cord blood banks allow people to save their childs cord blood and cord tissue for the future. They can be expensive for the initial setup, and they charge annual fees for cord blood storage. However, the benefits can outweigh the costs for parents with other children who have known illnesses that can be treated using cord blood. This type of banking ensures that a family maintains possession of their cord blood so that it can be used as needed by members of the specific family. The U.S. has over 25 private cord blood banks that families can use. If a family elects to use a private cord bank, then a medical carrier service will retrieve the cord blood from the hospital and transport it to the cord blood bank. The courier service assists in making transport more accessible to a wider range of families and eases the burden felt by new parents by checking off one activity from a new parents busy to-do list.

Public cord blood banks: Cord blood donations to public banks are frequently used for research. The banks also help people to obtain access to cord blood for transplants. Individuals donate their babys cord blood without charge, which provides other people the ability to receive much-needed treatment. Public cord banks located throughout North America allow more people to access these services.

Hybrid cord blood banks: Some banks offer public and private services. These banks store your childs blood for the future and accept cord blood donations for use by the public. Hybrid cord blood banks help people to access cord blood from various areas within the country as well as from the larger international cord blood banking system. Hybrid banks provide improved access to a wider range of available cord blood.

An autologous transplant or stem-cell transplant occurs when healthy stem cells from your body are used to help improve your bone marrow. Bone marrow can be found within your bones, and it helps to create red and white blood cells. An individual with weakened bone marrow faces life-threatening complications. An autologous transplant helps to address these concerns by placing previously removed stem cells back into your body.

The process is common for individuals that need cancer treatment such as chemotherapy. People who need chemotherapy will have some healthy stem cells removed and then undergo chemotherapy. Afterward, the healthy stem cells are replaced to help improve their bone marrow.

An autologous transplant shouldnt be confused with an allogeneic stem cell transplant. The main difference is that an allogeneic stem cell transplant comes from other people while an autologous stem cell transplant comes from yourself.

When researching cord blood banking, its common to have questions along the way. If you intend to give birth, consider the benefits of cord blood banking while speaking with the hospital and cord blood bank to understand the expected process. Ask about possible risks and prices before making a final decision.

Private cord blood banking can be expensive. One reason that cord blood banking has high costs is that its not usually covered by insurance. However, families with histories of certain illnesses have the possibility of getting a portion of the costs offset by insurance. Costs usually include initial storage fees, which are $1,000 or more, in addition to yearly storage fees. The storage fees range between $200 and $300 annually.

Not all hospitals offer cord blood banking procedures. The hospitals that do offer cord blood banking usually do not complete the banking procedure in-house. The hospitals and cord blood banks often work in tandem because the hospitals extract the cord blood from the umbilical cord while cord blood banks store the cord blood. See if the hospital youll be using provides the option of a cord blood procedure. Its common for a courier to transport the cord blood to a specified cord blood banking lab to complete the procedure.

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What is Cord Blood Banking? - Benzinga

Bone Marrow Stem Cells Comments Off on What is Cord Blood Banking? – Benzinga | August 26th, 2022

What Are Hematopoietic Stem Cells and Why Are They Important? Hematopietic stem cells (HSCs) are multipotent cells found in the blood and bone marrow with the ability to self-renew and differentiate into multiple cell types during bone marrow hematopoiesis. Clinicians use HSCs to replace or repopulate a patients blood as a form of regenerative medicine. Research into HSC development and aging facilitates better in vitro HSC expansion and broadens their potential for disease treatment, enhancing their clinical therapeutic effects.

How Hematopoietic Stem Cells DevelopHSCs begin their development during embryogenesis in the dorsal aortic tissue and are additionally found in the placenta, yolk sac, and fetal liver. This fetal hematopoiesis process is necessary to produce the blood cells required for tissue development while generating a pool of undifferentiated HSCs. At birth, these HSCs migrate into and populate the newly-formed bone marrow and maintain a steady state of self-renewal and differentiation.1 HSCs function by producing red blood cells, platelets, and white blood cells throughout life, maintaining their levels following bleeding and infection. HSCs generally give rise to partly differentiated but proliferative progenitors, which differentiate into mature cells. Because of this process, true HSCs are relatively rare in the human body.2

Using Hematopoietic Stem Cells for Research and TreatmentHematopoietic stem cell transplantsFor more than 60 years, hematopoietic stem cell transplants (HSCTs) have been the most common form of HSC therapy, and are a standard option for treating hematologic malignancies, immunodeficiency, and defective hematopoiesis disorders. HSCs are now derived from multiple sources, such as peripheral and cord blood and bone marrow. Before transplantation, the receiving patient must undergo severe immunosuppressive procedures to prevent rejection of the new stem cells.3

Hematopoietic stem cell isolationThe most common HSC isolation method involves removing blood cells from plasma using density gradient centrifugation followed by magnetic bead isolation using the CD34+ surface marker, a general marker for all hematopoietic progenitors. Using flow cytometry, scientists sort specific HSC cell types based on common cell surface markers.4 Clinicians then intravenously infuse these cells into the receiver patients marrow where they engraft and repopulate the blood and immune system. In blood cancers such as leukemias and lymphomas, restoration of the blood system by HSCT allows patients to receive high-dose chemotherapy treatments, ridding them of malignant cells. In patients with red blood cell conditions where continuous blood transfusions are not an option, such as thalassemia major, HSCT results in 80 percent disease-free survival.5

Hematopoietic stem cells in gene and tissue regeneration therapyBone marrow hematopoietic stem cells also differentiate into cells of other lineages, such as endothelial cells, cardiomyocytes, neural cells, and hepatocytes, in a process called transdifferentiation. Because adult stem cells are rare, understanding the mechanisms behind HSC transdifferentiation could provide an additional source of tissue-specific multipotent cells and influence future clinical methods for tissue regeneration. HSCs can also help repair injured organs by releasing regenerative cytokines and recruiting cells to the damage site.5 Some of the latest advances in HSC therapeutic research involve using methods such as CRISPR for correcting genetically-defective HSCs. These methods will allow a patient to receive their own genetically-compatible (syngeneic) HSCs. These are called allogeneic transplants and are more effective at avoiding graft-versus-host disease, a condition where transplants from a donor are rejected by the recipients body, leading to an immune response against other tissues and organs. Creating genetically-corrected induced pluripotent stem cells (iPSCs) from patient skin tissues and differentiating them into HSCs has also been an active area of research, although current methods remain costly and time-consuming.6 Further research is necessary to take advantage of these remarkable multipotent cells in disease therapies.

References

1. H.K. Mikkola, S.H. Orkin, The journey of developing hematopoietic stem cells, Development, 133(19):3733-44, 2006.

2. G.M. Crane et al., Adult haematopoietic stem cell niches, Nat Rev Immunol, 17(9):573-90, 2017.

3. S. Giralt, M.R. Bishop, Principles and overview of allogeneic hematopoietic stem cell transplantation, Cancer Treat Res, 144:1-21, 2009.

4. B. Kumar, S.S. Madabushi, Identification and isolation of mice and human hematopoietic stem cells, Methods Mol Biol, 1842:55-68, 2018.

5. J.Y. Lee, S.H. Hong, Hematopoietic stem cells and their roles in tissue regeneration, Int J Stem Cells, 13(1):1-12, 2020.

6. S. Demirci et al., Hematopoietic stem cells from pluripotent stem cells: Clinical potential, challenges, and future perspectives, Stem Cells Transl Med, 9(12):1549-57, 2020.

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Brush Up: Hematopoietic Stem Cells and Their Role in Development and Disease Therapy - The Scientist

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According to the National Cancer Institute, over 60,000 people will be diagnosed with leukemia this year and 24.000 will die. The NCI explains, "There is no standard staging system for leukemia. The disease is described as untreated, in remission, or recurrent," and while there's no way to prevent the cancer, there are lifestyle choices like not smoking that help reduce the risk. Read on to learn what experts say about leukemia and to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.

The Mayo Clinic says, "Leukemia is cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. Many types of leukemia exist. Some forms of leukemia are more common in children. Other forms of leukemia occur mostly in adults. Leukemia usually involves the white blood cells. Your white blood cells are potent infection fighters they normally grow and divide in an orderly way, as your body needs them. But in people with leukemia, the bone marrow produces an excessive amount of abnormal white blood cells, which don't function properly."

The National Cancer Institute says, "Leukemia is cancer that starts in the tissue that forms blood. Most blood cells develop from cells in the bone marrow called stem cells. In a person with leukemia, the bone marrow makes abnormal white blood cells. The abnormal cells are leukemia cells. Unlike normal blood cells, leukemia cells don't die when they should. They may crowd out normal white blood cells, red blood cells, and platelets. This makes it hard for normal blood cells to do their work. The four main types of leukemia are:6254a4d1642c605c54bf1cab17d50f1e

Acute lymphoblastic leukemia (ALL)

Acute myelogenous leukemia (AML)

Chronic lymphocytic leukemia (CLL)

Chronic myelogenous leukemia (CML)"

The Cleveland Clinic explains, "Leukemia is often considered a childhood illness. Even though it is one of the most common childhood cancers, the blood disorder cancer actually affects far more adults. According to the National Cancer Institute, leukemia is most frequently diagnosed among people between the ages of 65 and 74 years. The median age at diagnosis is 66. There are treatment options for patients of all ages, include chemotherapy and blood transfusions."

According to the Mayo Clinic, "Leukemia symptoms vary, depending on the type of leukemia. Common leukemia signs and symptoms include:

The Mayo Clinic states, "Factors that may increase your risk of developing some types of leukemia include:

Heather Newgen

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Sure Signs You Have Leukemia, Say Physicians Eat This Not That - Eat This, Not That

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MONDAY, Aug. 22, 2022 (HealthDay News) -- The U.S. Food and Drug Administration has approved Zynteglo (betibeglogene autotemcel), the first cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Zynteglo is a one-time, single-dose gene therapy product. Each dose of Zynteglo is customized and created using the patient's own bone marrow stem cells, which are genetically modified to produce functional beta-globin. The application was granted a rare pediatric disease voucher, as well as priority review, fast-track, breakthrough therapy, and orphan designations.

The approval was based on two multicenter clinical studies. Of 41 patients receiving Zynteglo, 89 percent achieved transfusion independence, defined as maintaining a predetermined level of hemoglobin without needing any red blood cell transfusions for at least 12 months. The most common adverse reactions seen with Zynteglo included reduced platelet and other blood cell levels, mucositis, febrile neutropenia, vomiting, fever, alopecia, nosebleed, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and itch.

Given the potential risk for blood cancer associated with this treatment, patients receiving Zynteglo should have their blood monitored for at least 15 years for evidence of cancer. The FDA says patients should also be monitored for hypersensitivity reactions during Zynteglo administration and for thrombocytopenia and bleeding.

Approval of Zynteglo was granted to bluebird bio.

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FDA Approves First Cell-Based Gene Therapy for Beta-Thalassemia - HealthDay News

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Clogging a proteins active site is a straightforward way to take it offline. Thats why the active site is often the first place drug designers look when designing new drugs, Reich explained. However, about eight years ago he decided to investigate compounds that could bind to other sites in an effort to avoid off-target effects.

As the group was investigating DNMT3A, they noticed something peculiar. While most of these epigenetic-related enzymes work on their own, DNMT3A always formed complexes, either with itself or with partner proteins. These complexes can involve more than 60 different partners, and interestingly, they act as homing devices to direct DNMT3A to control particular genes.

Early work in the Reich lab, led by former graduate student Celeste Holz-Schietinger, showed that disrupting the complex through mutations did not interfere with its ability to add chemical markers to the DNA. However, the DNMT3A behaved differently when it was on its own or in a simple pair; it wasnt to stay on the DNA and mark one site after another, which is essential for its normal cellular function.

Around the same time, the New England Journal of Medicine ran a deep dive into the mutations present in leukemia patients. The authors of that study discovered that the most frequent mutations in acute myeloid leukemia patients are in theDNMT3Agene. Surprisingly, Holz-Schietinger had studied the exact same mutations. The team now had a direct link between DNMT3A and the epigenetic changes leading to acute myeloid leukemia.

Reich and his group became interested in identifying drugs that could interfere with the formation of DNMT3A complexes that occur in cancer cells. They obtained a chemical library containing 1,500 previously studied drugs and identified two that disrupt DNMT3A interactions with partner proteins (protein-protein inhibitors, or PPIs).

Whats more, these two drugs do not bind to the proteins active site, so they dont affect the DNMT1 at work in all of the bodys other cells. This selectivity is exactly what I was hoping to discover with the students on this project, Reich said.

These drugs are more than merely a potential breakthrough in leukemia treatment. They are a completely new class of drugs: protein-protein inhibitors that target a part of the enzyme away from its active site. An allosteric PPI has never been done before, at least not for an epigenetic drug target, Reich said. It really put a smile on my face when we got the result.

This achievement is no mean feat. Developing small molecules that disrupt protein-protein interactions has proven challenging, noted lead authorJonathan Sandovalof UC San Francisco, a former doctoral student in Reichs lab. These are the first reported inhibitors of DNMT3A that disrupt protein-protein interactions.

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A new kind of chemo - University of California

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