In the present study, we derived two particularly noteworthy results. First, nearly half of the institutions that responded to the study were either currently providing UCB to private banks during the study period or had done so in the past. Second, some institutions were found to provide UCB not only to private banks but also to companies, research institutions, and medical treatment facilities.

During the present study, the APHSCT, along with related ministerial ordinances and guidelines, stipulated how public banks preserve and manage UCB. However, during the study period, these laws and regulations did not require the institutions that handled childbirth to keep records, except when providing UCB to public banks. Consequently, no one knew how many institutions handling childbirth supplied UCB to private banks or the status of UCB distribution. The present study determined that 34.4% of institutions handling childbirth currently provide UCB to private banks, while 16.1% of institutions did so in the past. Our study reported for the first time that these percentages far outstrip those for UCB supply to public banks (6.1% and 8.0%, respectively). These low percentages may be related to the low number of institutions handling childbirth in Japan partnered with public banks (96 institutions as of January 18, 2021) [14,15,16,17,18,19].

However, from the standpoint of appropriate collection, safe preservation, and effective usage of UCB, public and private banks should be regulated according to more uniform standards. More than one-fourth of institutions that provide or have provided UCB to private banks did not provide explanations about UCB collection to UCB donors, while nearly 20% of institutions did not obtain consent. Donors of UCB choose to have their UCB preserved and are also users of UCB who entrust their UCB to private banks, a state of affairs that may lead to the opinion that it is not that important for institutions handling childbirth to provide explanations or obtain consent. However, an MHLW survey reported that private banks do not provide sufficient explanations to users in advance [20]. This state of affairs may be related to the absence of regulations in private banks in Japan.

Even before we demonstrated problems with private banks in Japan in the present study with empirical data, these problems were already known anecdotally, which led many academic associations to issue warnings. In 2002, the Japan Society for Hematopoietic Cell Transplantation issued a statement declaring that private banks were almost completely ineffective, except in cases such as patients with refractory blood diseases within ones own family and that regulations were necessary to ensure proper technical guidelines and safety [21]. In addition, the Japan Association of Obstetricians and Gynecologists declared in 2002 that sufficient understanding was necessary regarding the status and background of private storage of UCB and that careful steps were required to ensure that private banks do not simply use UCB for profit [22].

However, as we analyzed the results of the present study, a relevant concern came to pass. In 2017, physicians who administered UCB to patients without notifying government authorities were found guilty of violating the Act on the Safety of Regenerative Medicine, with the vendor who sold the UCB charged as an accomplice [23, 24]. The UCB sold by the vendor leaked from a private bank that had gone bankrupt in 2009. However, the charge in this case was providing regenerative medicine to patients without reporting it to the MHLW; there was no law targeting the sale of the leaked UCB itself, which was, therefore, beyond the scope of legal penalty [25].

Spurred by the case described above, the MHLW conducted a survey of private UCB banks in Japan [20]. Of the seven vendors whose activities could be confirmed at the time of the survey, six responded; one of these vendors only distributed UCB without preserving it. The UCB held by the remaining five vendors constituted a supply for a total of 45,800 people; roughly 2,100 peoples worth of UCB had not been disposed after the vendors contracts with the donors had ended. One vendor provided UCB to a third party (roughly 160 times). The three vendors involved in the above case later went out of business [26].

Taking the case seriously, the MHLW revised the APHSCT to generally prohibit the collection, preparation, storage, testing, and delivery of UCB for transplantation as a business by entities other than public banks. The revision also stipulated that UCB for transplantation may not be delivered by anyone for commercial purposes. However, these prohibitions do not apply when a public bank delivers UCB, when UCB is used in the treatment of a blood relative to the donor, or when approval is granted by the MHLW. Violations of these prohibitions are subject to criminal penalties. Consequently, the two private banks that obtained approval from the MHLW were permitted to continue their activities.

However, regardless of legal permission, there is still the question of whether private UCB banks, which handle UCB for profit, are ethically permissible. For example, the 2004 European Commissions Group on Ethics in Science and New Technologies stated that while they did not completely disavow for-profit biobank activities, these activities engender ethical criticism. The group also stated that the human body in principle is not an object of commercial value and recommended that private biobank activities operate under strict conditions such as appropriate management by regulatory authorities [27]. Meanwhile, a non-Japanese study has reported that the possibility of UCB being used 20years later by the person who requested its preservation or by their family is an incredibly low 0.040.0005% [28]. The extent to which this information is explained to potential private bank users is unknown. In fact, the previously cited survey by the MHLW indicated that the role of public UCB banks and the actual utility of the UCB stored in the private banks were not sufficiently explained to users [20]. Future research must thoroughly examine the status of UCB private banks following revision of the law and compare the results of this examination to the findings of the present study.

A small number of institutions handling childbirth surveyed in the present study responded that they currently provide or used to provide UCB to medical treatment facilities (2.6%), research institutions (5.9%), companies (2.2%), or foreign medical treatment facilities, research institutions, or companies (0.3%). Some institutions handling childbirth also either currently store or used to store UCB themselves for treatment or research (2.3% and 3.2%, respectively). This aspect of the status of UCB distribution has never been demonstrated in a previous study.

Since the revision of the APHSCT, the delivery of UCB for transplantation has been strictly prohibited except in the cases of provision to a public bank, provision to a private bank approved by the MHLW, and use for treatment by a blood relative. Thus, it is currently considered illegal for institutions handling childbirth to deliver UCB to other facilities domestically or internationally or to store UCB themselves for treatment purposes. However, the revised law still does not apply to the handling of UCB for research purposes, that is, basic studies and the development of treatments. In addition, while there are laws and local ordinances that call for the incineration or burial of UCB according to specific methods, these regulations generallydo not cover the delivery of UCB for research purposes.

At a glance, there would seem to be no problem with an institution that handles childbirth providing UCB to a third party or storing UCB itself for research purposes. However, the results of the present study, which found that a certain number of institutions handling childbirth do not provide explanations or obtain consent when UCB is harvested from private bank users, and the results of the above-cited MHLW survey, which found that private banks also fail to provide users with sufficient explanations, cast doubt amidst the absence of relevant laws and regulations as to how much has been suitably explained to UCB donors when they consent to be third-party UCB donors.

We did not determine what sort of explanations institutions handing childbirth give when they deliver UCB to other institutions or store it themselves for research purposes, nor did we determine methods for obtaining consent, as we felt these fell outside the aim of the present study. Future studies must answer these questions and evaluate if there truly is no problem with the current state of affairs in Japan in the absence of rules regarding the harvest or delivery of UCB for research purposes by institutions handling childbirth.

The present study had several limitations. First, the response rate was only 36.7%, which is not at all high. However, the percentages of institutions handling childbirth by type that responded to our survey are roughly consistent with those of Japanese medical treatment facilities overall [29], implying that our results are representative to some extent. Of course, we cannot rule out the effect of non-responder bias. However, the present study can be considered sufficiently significant because this is the first study to determine the status of UCB delivery by Japanese institutions handling childbirth to private banks, other companies, research institutions, and medical treatment facilities. The 3,277 facilities included in this study represent 99.9% of childbirth facilities in Japan. The total number of facilities in Japan is approximately 3,280. Of which 1,084 facilities responded that they handled childbirth. A simple calculation from the actual number of births in 2016 (976,978 births), a year before this study was conducted [30], allowed us to estimate that the facilities included in our study handled a total of 322,879 births. The number of UCBs managed by these facilities can be considered significant. In addition, by determining the status of UCB delivery prior to revision of the APHSCT, we have made it possible to determine the effects of APHSCT via comparisons with post-revision survey results.

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Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan - BMC Medical Ethics -...

IPS Cell Therapy Comments Off on Current status of umbilical cord blood storage and provision to private biobanks by institutions handling childbirth in Japan – BMC Medical Ethics -… | September 19th, 2022

Adult stem cells, also called somatic stem cells, are undifferentiated cells that are found in many different tissues throughout the body of nearly all organisms, including humans. Unlike embryonic stem cells, which can become any cell in the body (called pluripotent), adult stem cells, which have been found in a wide range of tissues including skin, heart, brain, liver, and bone marrow are usually restricted to become any type of cell in the tissue or organ that they reside (called multipotent). These adult stem cells, which exist in the tissue for decades, serve to replace cells that are lost in the tissue as needed, such as the growth of new skin every day in humans.

Scientists discovered adult stem cells in bone marrow more than 50 years ago. These blood-forming stem cells have been used in transplants for patients with leukemia and several other diseases for decades. By the 1990s, researchers confirmed that nerve cells in the brain can also be regenerated from endogenous stem cells. It is thought that adult stem cells in a variety of different tissues could lead to treatments for numerous conditions that range from type 1 diabetes (providing insulin-producing cells) to heart attack (repairing cardiac muscle) to neurological disease (regenerating lost neurons in the brain or spinal cord).

Efforts are underway to stimulate these adult stem cells to regenerate missing cells within damaged tissues. This approach will utilize the existing tissue organization and molecules to stimulate and guide the adult stem cells to correctly regenerate only the necessary cell types. Alternatively, the adult stem cells could be isolated from the tissue and grown outside of the body, in cultures. This would allow the cells to be easily manipulated, although they are often relatively rare and difficult to grow in culture.

Because the isolation of adult stem cells does not result in the destruction of human life, research involving adult stem cells does not raise any of the ethical issues associated with research utilizing human embryonic stem cells. Thus, research involving adult stem cells has the potential for therapies that will heal disease and ease suffering, a major focus of Notre Dames stem cell research. Combined with our efforts with induced pluripotent stem (iPS) cells, the Center for Stem Cells and Regenerative Medicine will advance the Universitys mission to ease suffering and heal disease.

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Adult Stem Cells // Center for Stem Cells and Regenerative Medicine ...

Cardiac Stem Cells Comments Off on Adult Stem Cells // Center for Stem Cells and Regenerative Medicine … | September 19th, 2022

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Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram | Scientific...

Bone Marrow Stem Cells Comments Off on Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram | Scientific… | September 19th, 2022

ThisBone Marrow MarketReport provides details on Recent New Developments, Trade Regulations, Import-Export Analysis, Production Analysis, Value Chain Optimization, Market Share, Impact of Domestic and Localized Market Players, Analyzes opportunities in terms of emerging revenue pockets, changing market regulations, strategic market growth analysis, market size, market category growth, niche and application dominance, product endorsements, product launches, geographic expansions , technological innovations in the market.For more information on the bone marrow market, please contact Data Bridge Market Research for a summary of theanalyst, our team will help you make an informed market decision to achieve market growth.

Bone Marrow Market is expected to experience market growth during the forecast period of 2021 to 2028. Data Bridge Market Research analyzes that the market is growing with a CAGR of 5.22% during the forecast period of 2021 to 2028 and it is projected to reach USD 13,899.60 Million by 2028. The increasing number of bone marrow diseases will help accelerate the growth of the bone marrow market.Bone marrow transplant also called hematopoietic stem cell.It is a soft vascular tissue present inside the long bones.It includes two types of stem cells, namely hematopoietic and mesenchymal stem cells.The bone marrow is primarily responsible for hematopoiesis (blood cell formation), lymphocyte production, and fat storage.

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The main factors driving the growth of the bone marrow market during the forecast period are the growth in the incidence of non-Hodgkins and Hodgkins lymphoma, thalassemia, and leukemia, as well as common bone marrow diseases worldwide, developments in technology and improvements.in health infrastructure.In addition, advanced signs of bone marrow transplantation for cardiac and neural disorders, increased funding for logistics services, and rising health care spending per capita are some of the other factors expected to further drive growth. growth of the bone marrow market in the coming years.years.However, the high costs of treatment,

Key Players Covered in the Bone Marrow Market Report are AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc., Astellas Pharma Inc., diaDexus, Illumina, Inc., QIAGEN, F Hoffmann-La Roche Ltd, Sanofi, Stryker Corporation, PromoCell GmbH, STEMCELL Technologies Inc., Lonza, ReachBio LLC, AllCells, ATCC, Lifeline Cell Technology, Conversant bio, HemaCare, Mesoblast Ltd., Merck KGaA, Discovery Life Sciences, ReeLabs Pvt. Ltd., Gamida Cell, among others national and global players.Market share data is available separately for Global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA), and South America.DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

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Bone MarrowMarket Scope and Market Size

The bone marrow market is segmented based on transplant type, disease indication, and end user.Growth between these segments will help you analyze weak growth segments in industries and provide users with valuable market overview and market insights to help them make strategic decisions to identify leading market applications.

Country-level analysis of thebone marrow market

The bone marrow market is analyzed and information is provided on market size and trends by country, transplant type, disease indication, and end user, as mentioned above.Countries Covered in Bone Marrow Market Report are USA, Canada, and Mexico, North America, Germany, France, UK, Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, the Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific region (APAC), Saudi Arabia, United Arab Emirates , South Africa, Egypt, Israel, Rest of the Middle East and Africa (MEA) under Middle East and Africa (MEA), Brazil,

Europe dominates the bone marrow market due to the proliferation of innovative health centers.Furthermore, the health systems have introduced bone marrow transplantation in their contributions and state-of-the-art public facilities that will further drive the growth of the bone marrow market in the region during the forecast period.North America is expected to witness significant growth in the bone marrow market due to increasing cases of chronic diseases such as blood cancer.In addition, the increase in the geriatric population is one of the factors that is expected to drive the growth of the bone marrow market in the region in the coming years.

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The country section of the Bone Marrow market report also provides individual market impact factors and regulatory changes in the country market that affect current and future market trends.Data points such as consumption volumes, production sites and volumes, import and export analysis, price trend analysis, raw material cost, Downstream and Upstream value chain analysis are some of the main indicators used to forecast the scenario. of the market for each country.Additionally, the presence and availability of global brands and the challenges they face due to significant or rare competition from local and national brands,

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Bone Marrow market estimated to reach US$13899.60 Million during the forecast period - Digital Journal

Bone Marrow Stem Cells Comments Off on Bone Marrow market estimated to reach US$13899.60 Million during the forecast period – Digital Journal | September 19th, 2022

Our work on an enzyme that is mutated in leukemia patients has led to the discovery of an entirely new way of regulating this enzyme, as well as new molecules that are more effective and less toxic to human cells, said Norbert Reich, a distinguished professor at the University of California, Santa Barbara, and the corresponding author of the study.

A cells epigenome is copied and maintained by an enzyme called DNMT1. For instance, this enzyme ensures that a dividing liver cell produces two liver cells rather than a brain cell.

However, some cells need to undergo differentiation to become new types of cells. For instance, bone marrow stem cells can developall the various blood cell types, which are incapable of self-replication. DNMT3A, another enzyme, manages this.

This is not a problem until a dysfunction of DNMT3A results in the production of abnormal blood cells from bone marrow. This is a prominent factor in the development of several types of leukemia as well as other cancers.

Most cancer medications are intended to attack cancer cells while only leaving healthy cells. But this is quite a challenging process; therefore, most have severe side effects.

Current leukemia medications, such as Decitabine, bind to DNMT3A in a way that disables it. So that they slow the progression of the disease by obstructing the enzyme's active site, preventing it from continuing its function.

Unfortunately, the active site of DNMT3A is virtually identical to that of DNMT1, therefore, the medication blocks epigenetic regulation in patients' 30 to 40 trillion cells. This leads to off-target toxicity- one of the drug industry's largest bottlenecks.

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Researchers discover a new class of medications that offer a safer treatment for leukemia - Interesting Engineering

Bone Marrow Stem Cells Comments Off on Researchers discover a new class of medications that offer a safer treatment for leukemia – Interesting Engineering | September 19th, 2022

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

I wanted to see if I still could: MS patient raises charity cash with gruelling challenge

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

Bone Marrow Stem Cells Comments Off on ‘Best thing I ever did’: Newmachar mum showing promising signs after 47000 MS treatment in Mexico – The Press & Journal | September 19th, 2022

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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Radical lupus treatment uses CAR T-cell therapy developed for cancer - New Scientist

Bone Marrow Stem Cells Comments Off on Radical lupus treatment uses CAR T-cell therapy developed for cancer – New Scientist | September 19th, 2022

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.

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

Bone Marrow Stem Cells Comments Off on Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan – Cureus | September 19th, 2022

Positive Opinion Based on Landmark ZUMA-7 Study in Which 41% of Patients Demonstrated Event-Free Survival at Two Years versus 16% for Standard of Care -

SANTA MONICA, Calif.--(BUSINESS WIRE)--Kite, a Gilead Company (Nasdaq: GILD), today announces that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Yescarta (axicabtagene ciloleucel) for adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. If approved, Yescarta will be the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. Although 60% of newly diagnosed LBCL patients will respond to their initial treatment, 40% will relapse or will not respond and need 2nd line treatment.

At Kite, we are committed to bringing the curative potential of cell therapy to the world, and changing the way cancer is treated, said Christi Shaw, CEO, Kite. Todays positive CHMP opinion brings us a step closer to utilizing cell therapy earlier in the treatment journey, potentially transforming the standard of care for the most common and aggressive form of non-Hodgkin lymphoma.

The European Commission will review the CHMP opinion, and a final decision on the marketing authorization is expected in the coming months.

For people with DLBCL and HGBL who do not respond to first-line treatment or have an early relapse, outcomes are often poor and there are limited curative treatment options for these patients, said Marie Jos Kersten, Professor of Hematology at Amsterdam University Medical Centers, Amsterdam. If approved, axicabtagene ciloleucel may offer a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly, in a randomized trial of axicabtagene ciloleucel versus the current standard of care, quality of life also showed greater improvement in the experimental arm.

The positive opinion for Yescarta is based on the primary results of the landmark Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus standard of care (SOC) in second-line LBCL. Results demonstrated that at a median follow-up of two years, Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001) over the current SOC (8.3 months v 2.0 months). Additionally, Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%). Improvements in EFS with Yescarta were consistent across key patient subgroups, including elderly patients (HR: 0.28 [95% CI: 0.16-0.46]), primary refractory patients (HR: 0.43 [95% CI: 0.32- 0.57]), high-grade B cell lymphoma including double-hit and triple-hit lymphoma patients (HGBL; HR: 0.28 [95% CI: 0.14-0.59]), and double expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).

In a separate, secondary analysis of Patient-Reported Outcomes (PROs) published in Blood patients receiving Yescarta and eligible for the PROs portion of the study (n=165) showed statistically significant improvements in Quality of Life (QoL) at Day 100 compared with those who received SOC (n=131), using a pre-specified analysis for three PRO-domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QOL, and EQ-5D-5L visual analog scale [VAS]). There was also a trend toward faster recovery to baseline QoL in the Yescarta arm versus SOC.

In the ZUMA-7 trial, Yescarta had a manageable safety profile that was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, Grade 3 cytokine release syndrome (CRS) and neurologic events were observed in 6% and 21% of patients, respectively. No Grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had high-grade events, mostly cytopenias (low blood counts).

About ZUMA-7

ZUMA-7 is an ongoing, randomized, open-label, global, multicenter (US, Australia, Canada, Europe, Israel) Phase 3 study of 359 patients at 77 centers, evaluating the safety and efficacy of a single-infusion of Yescarta versus current SOC for second-line therapy (platinum-based salvage combination chemotherapy regimen followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The primary endpoint is event free survival (EFS) as determined by blinded central review, and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety.

About Yescarta

Yescarta was first approved in Europe in 2018 and is currently indicated for three types of blood cancer: Diffuse Large B-Cell Lymphoma (DLBCL); Primary Mediastinal Large B-Cell Lymphoma (PMBCL); and Follicular Lymphoma (FL). For the full European Prescribing Information, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta

Please see full US Prescribing Information, including BOXED WARNING and Medication Guide.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including Grade 3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including Grade 3 in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and the median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS ( 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Ensure that 2 doses of tocilizumab are available prior to YESCARTA infusion. Monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life-threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range:1- 133 days) and the median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL.

The most common neurologic toxicities ( 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41), and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in a higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset of and decrease the duration of CRS.

Monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS

Because of the risk of CRS and neurologic toxicities, YESCARTA is available only through a restricted program called the YESCARTA and TECARTUS REMS Program which requires that: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after YESCARTA infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer YESCARTA are trained in the management of CRS and neurologic toxicities. Further information is available at http://www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS

Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of YESCARTA.

SERIOUS INFECTIONS

Severe or life-threatening infections occurred. Infections (all grades) occurred in 45% of patients with NHL; Grade 3 infections occurred in 17% of patients, including Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of all patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. Grade 3 cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES

Secondary malignancies may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS

The most common non-laboratory adverse reactions (incidence 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with an unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.

The most common adverse reactions (incidence 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with an unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

The most common non-laboratory adverse reactions (incidence 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with an unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kites singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. For more information on Kite, please visit http://www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials, including those involving Yescarta; uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the European Commission may not grant marketing authorization for Yescarta for use in second-line DLBCL and HGBL in a timely manner or at all; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use; the risk that physicians may not see the benefits of prescribing Yescarta for the treatment of LBCL; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gileads Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

U.S. Prescribing Information for Yescarta including BOXED WARNING, is available at http://www.kitepharma.com and http://www.gilead.com .

Kite, the Kite logo, Yescarta and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies .

View source version on businesswire.com: https://www.businesswire.com/news/home/20220916005209/en/

Jacquie Ross, Investorsinvestor_relations@gilead.com

Anna Padula, Mediaapadula@kitepharma.com

Source: Gilead Sciences, Inc.

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Kite's CAR T-cell Therapy Yescarta First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and...

Cardiac Stem Cells Comments Off on Kite’s CAR T-cell Therapy Yescarta First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and… | September 19th, 2022

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CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease - Cardiovascular Diabetology - Cardiovascular...

Cardiac Stem Cells Comments Off on CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease – Cardiovascular Diabetology – Cardiovascular… | September 19th, 2022

IMAC Holdings, Inc.

BRENTWOOD, Tenn., Sept. 09, 2022 (GLOBE NEWSWIRE) -- IMAC Holdings, Inc. (Nasdaq: BACK) (IMAC or the Company), today announces it has completed the third cohort of its Phase 1 clinical trial for its investigational compound utilizing umbilical cord-derived allogenic mesenchymal stem cells for the treatment of bradykinesia due to Parkinsons disease.

The third cohort consists of five patients with bradykinesia due to Parkinsons disease receiving an intravenous infusion of a high concentration stem cell treatment. The third and final cohort of the Phase 1 clinical trial was completed on Tuesday, September 6, 2022.

About IMACs Phase 1 Clinical Trial

The Phase 1 clinical trial, consisting of a 15-patient dose escalation safety and tolerability study, is being conducted at three of IMACs clinical centers in Chesterfield, Missouri, Paducah, Kentucky, and Brentwood, Tennessee. The trial is divided into three groups: 1) five patients with bradykinesia due to Parkinsons disease received a low concentration dose, intravenous infusion of stem cells, 2) five received a medium concentration intravenous dose, 3) and five received a high concentration intravenous dose. All groups will be subsequently tracked for 12 months. IMACs medical doctors and physical therapists at the clinical sites have been trained to administer the treatment and manage the therapy. Ricardo Knight, M.D., M.B.A., who is medical director of the IMAC Regeneration Center of Chicago, is the trials principal investigator.

The Institute of Regenerative and Cellular Medicine serves as the trials independent investigational review board, while Regenerative Outcomes provides management of the study. Further details of the trial can be found at clinicaltrials.gov.

About Bradykinesia Due to Parkinsons Disease

In addition to unusually slow movements and reflexes, bradykinesia may lead to limited ability to lift arms and legs, reduced facial expressions, rigid muscle tone, a shuffling walk, and difficulty with repetitive motion tasks, self-care, and daily activities. Parkinsons disease is the typical culprit of bradykinesia, and as it progresses through its stages, a persons ability to move and respond declines.

Story continues

According to Zion Market Research, the global Parkinsons disease therapeutics market was $2.61 billion in 2018 and is expected to grow to $5.28 billion by 2025. The Parkinsons Disease Foundation estimates that nearly 10 million people are suffering from Parkinsons disease, and almost 60,000 new cases are reported annually in the U.S.

About IMAC Holdings, Inc.

IMAC Holdingsowns and manages health and wellness centers that deliver sports medicine, orthopedic care, and restorative joint and tissue therapies for movement restricting pain and neurodegenerative diseases.IMACis comprised of three business segments: outpatient medical centers, The Back Space, and a clinical research division. With treatments to address both young and aging populations,IMAC Holdingsowns or manages outpatient medical clinics that deliver regenerative rehabilitation services as a minimally invasive approach to acute and chronic musculoskeletal and neurological health problems. IMACs The Back Company retail spinal health and wellness treatment centers deliver chiropractic care within Walmart locations. IMACs research division is currently conducting a Phase I clinical trial evaluating a mesenchymal stem cell therapy candidate for bradykinesia due to Parkinsons disease. For more information visitwww.imacholdings.com.

# # #

Safe Harbor Statement

This press release contains forward-looking statements. These forward-looking statements, and terms such as anticipate, expect, believe, may, will, should or other comparable terms, are based largely on IMAC's expectations and are subject to a number of risks and uncertainties, certain of which are beyond IMAC's control. Actual results could differ materially from these forward-looking statements as a result of, among other factors, risks and uncertainties associated with its ability to raise additional funding, its ability to maintain and grow its business, variability of operating results, its ability to maintain and enhance its brand, its development and introduction of new products and services, the successful integration of acquired companies, technologies and assets, marketing and other business development initiatives, competition in the industry, general government regulation, economic conditions, dependence on key personnel, the ability to attract, hire and retain personnel who possess the skills and experience necessary to meet customers requirements, and its ability to protect its intellectual property. IMAC encourages you to review other factors that may affect its future results in its registration statement and in its other filings with the Securities and Exchange Commission. In light of these risks and uncertainties, there can be no assurance that the forward-looking information contained in this press release will in fact occur.

IMAC Press Contact:

Laura Fristoe

lfristoe@imacrc.com

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IMAC Holdings, Inc. Announces Completion of Third Cohort of its Phase 1 Clinical Study of Umbilical Cord-Derived Mesenchymal Stem Cells for the...

Spinal Cord Stem Cells Comments Off on IMAC Holdings, Inc. Announces Completion of Third Cohort of its Phase 1 Clinical Study of Umbilical Cord-Derived Mesenchymal Stem Cells for the… | September 11th, 2022

A person with SMA may find it challenging to stand up, walk, control their head movements, and in some cases, even breathe and swallow

Spine. Image courtesy Pearson Scott Foresman/Wikimedia Commons

Spinal muscular atrophy (SMA) is a severe genetic condition that targets motor neurons in the central nervous system (CNS), resulting in progressive muscle atrophy, weakness, and paralysis. It is a group of genetic disorders in which a person cannot control the movement of their muscles due to a loss of nerve cells in the spinal cord and brain stem. A person with SMA may find it challenging to stand up, walk, control their head movements, and in some cases, even breathe and swallow. Some forms of SMA are present at birth, while others develop over time. Some have an impact on life expectancy.

SMA can be clinically divided into five subtypes. The most severe type is SMA type 0, appearbefore birth, can be fatal before or after birth within the first year of life. Type 1 SMA also called infantile-onset, is the most common type of SMA, accounting for 60% cases, which appears in infants and causes them to die or become dependent on a ventilator by the age of two. Children with SMA type 2 are sitters, while those with type 3 can walk on their own for a while before becoming wheelchair-bound. SMA type 4 develops in adults and causes later-life progressive weakness.

SMA is the most frequent cause of death in the infantile age group, occurring in one in 10,000 live births. However, the SMA carrier frequency was 1 in 38 in a recent Indian study. Children with SMA can currently receive supportive care in India that includes assisted ventilation, feeding, physiotherapy, orthotics, and spine stabilization.

What causes SMA?

SMA is caused by a very specific genetic mutation in a gene called theSMN1 gene. SMN is that protein that play a critical role in the survival of the nerve cells that control muscles. (SMN) protein keeps motor neurons healthy and functioning normally. The loss of motor neurons in the spinal cord caused by SMA patients, and insufficient levels of the SMN protein results in skeletal muscle weakness and wasting.

SMA patients gradually lose their ability to control their muscles movement and strength. The muscles closest to the torso and neck are frequently severely affected by the disease. Some SMA patients never sit, stand, or walk. Other signs of SMA include tongue fasciculation, a bell-shaped chest (caused by muscle weakness), weak cough, difficulty breathing , choking or trouble swallowing, weak sucking and labored breathing during feeding.

How is SMA diagnosed?

The diagnosis of spinal muscular atrophy depends on the type of SMA a person has and age of onset. The path to diagnosis for infants and children with more severe forms of SMA frequently starts when a parent or medical professional notices unusual muscle weakness (hypotonia). People with adult-onset SMA types, such as type 4, might begin the diagnosis process after observing minor symptoms like hand tremors.

Physical exam

A physical examination is required to identify the presence of symptoms like muscle weakness or a lack of reflexes in cases where a new-born is not screened for SMA at birth. A primary care physician or a neurologist could perform this.

Family medical history

As part of your or your childs physical examination, a thorough review of the patients family history is necessary to determine whether there have ever been any instances of neuromuscular disease in the family. If the physical examination and family history raise suspicion of SMA, genetic testing will likely be the next step.

Genetic testing

Through molecular genetic testing, which requires a blood sample, SMA is identified. A single gene is examined for mutations linked to a genetic disease in molecular genetic testing.

Importance of early diagnosis

A patient with SMA must first undergo a higher level of cognitive evaluation. The clinician should assess the patient for weakness before concentrating solely on SMA. A muscle biopsy could be the next step in the evaluation to more precisely distinguish between muscle weakness and nerve weakness. Finally, the clinician would probably identify this patients SMA based on the results of the combined muscle biopsy and electrode diagnostics.

If a diagnosis is made early, the individual has access to the tools and the resources that medical science has developed over the last number of years to assist optimal functioning.

The standard method for diagnosing SMA is molecular genetic testing. SMA should be given early consideration in any infant with weakness or hypotonia due to the effectiveness of molecular testing and high frequency of SMA in the hypotonic infant. All other infant causes of hypotonic weakness are included in the differential diagnosis of severe forms of SMA.

SMA is inherited in an autosomal recessive manner. Each pregnancy of a couple who have had a child with SMA has an approximately 25 per cent chance of producing an affected child. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the diagnosis of SMA has been confirmed by molecular genetic testing in an affected family member.

Currently, there are several SMA treatments that have received FDA approval including Risdiplam (Evrysdi), Onasemnogene abeparvovec-xioi (Zolgensma) and Nusinersen (Spinraza). These targeted treatments may prevent the development or slow the progression of some features of SMA.

The severity of the disease varies depending on the type of SMA, with more severe subtypes needing more aggressive treatment. Proactive care and treatment decision-making by the multidisciplinary team and family are of paramount importance.

The author is MBBS, DCH, MRCPCH, Fellowship Pediatric Genetics, Consultant Clinical Geneticist, Salem Genetics Centre. Views are personal.

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Spinal Muscular Atrophy: Causes and importance of early diagnosis for proactive management - Firstpost

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Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials...

IPS Cell Therapy Comments Off on Clinical translation of stem cell therapy for spinal cord injury still premature: results from a single-arm meta-analysis based on 62 clinical trials… | September 11th, 2022

DUBLIN--(BUSINESS WIRE)--The "Induced Pluripotent Stem Cells Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)" report has been added to ResearchAndMarkets.com's offering.

The Induced Pluripotent Stem Cells Market is projected to register a CAGR of 8.4% during the forecast period (2022 to 2027).

Companies Mentioned

Key Market Trends

The Drug Development Segment is Expected to Hold a Major Market Share in the Induced Pluripotent Stem Cells Market.

By application, the drug development segment holds the major segment in the induced pluripotent stem cell market. Various research studies focusing on drug development studies with induced pluripotent stem cells have been on the rise in recent years.

For instance, an article titled "Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening" published in the International Journal of Molecular Science in October 2020 discussed the broad use of iPSC derived cardiomyocytes for drug development in terms of adverse drug reactions, mechanisms of cardiotoxicity, and the need for efficient drug screening protocols.

Another article published in the Journal of Cells in December 2021 titled "Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform-A Cardiac Perspective" focused on methods to reprogram somatic cells into human induced pluripotent stem cells and the solutions to overcome the immaturity of the human induced pluripotent stem cells derived cardiomyocytes to mimic the structure and physiological properties of adult human cardiomyocytes to accurately model disease and test drug safety. Thus, this increase in the research of induced pluripotent stem cells for drug development and drug modeling is likely to propel the segment's growth over the study period.

Furthermore, as per an article titled "Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells" published in the Multi-Disciplinary Publishing Institute journal of Cells in March 2022, preserved differentiation and physiological function, amenability to genetic manipulation via tools such as CRISPR/Cas9, and availability for high-throughput screening, make induced pluripotent stem cell systems increasingly attractive for both mechanistic studies of disease and the identification of novel therapeutics.

North America is Expected to Hold a Significant Share in the Market and Expected to do Same in the Forecast Period

The rise in the adoption of highly advanced technologies and systems in drug development, toxicity testing, and disease modeling coupled with the growing acceptance of stem cell therapies in the region are some of the major factors driving the market growth in North America.

The United States Food and Drug Administration in March 2022 discussed the development of strategies to improve cell therapy product characterization. The agency focused on the development of improved methods for testing stem cell products to ensure the safety and efficacy of such treatments when used as therapies.

Likewise, in March 2020, the Food and Drug Administration announced that ImStem drug IMS001, which uses AgeX's pluripotent stem cell technology, would be available for the treatment of multiple sclerosis. Similarly, REPROCELL introduced a customized iPSC generation service in December 2020, as well as a new B2C website to promote the "Personal iPS" service. This service prepares and stores an individual's iPSCs for future injury or disease regeneration treatment.

Thus, the increasing necessity for induced pluripotent stem cells coupled with increasing investment in the health care department is known to propel the growth of the market in this region.

Key Topics Covered:

1 INTRODUCTION

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS

4.1 Market Overview

4.2 Market Drivers

4.2.1 Increase in Research and Development Activities in Stem Cells Therapies

4.2.2 Surge in Adoption of Personalized Medicine

4.3 Market Restraints

4.3.1 Lack of Awareness Regarding Stem Cell Therapies

4.3.2 High Cost of Treatment

4.4 Porter's Five Force Analysis

5 MARKET SEGMENTATION

5.1 By Derived Cell Type

5.2 Application

5.3 End User

5.4 Geography

6 COMPETITIVE LANDSCAPE

6.1 Company Profiles

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

For more information about this report visit https://www.researchandmarkets.com/r/ylzwhr

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Global Induced Pluripotent Stem Cells Market (2022 to 2027) - Growth, Trends, Covid-19 Impact and Forecasts - ResearchAndMarkets.com - Business Wire

IPS Cell Therapy Comments Off on Global Induced Pluripotent Stem Cells Market (2022 to 2027) – Growth, Trends, Covid-19 Impact and Forecasts – ResearchAndMarkets.com – Business Wire | September 11th, 2022

MELBOURNE, Australia--(BUSINESS WIRE)--Propanc Biopharma, Inc. (OTC Pink: PPCB) (Propanc or the Company), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, today announced significant effects of PRP against the tumor microenvironment and pre-metastatic niche has been reported by the Companys joint researcher, Mrs. Beln Toledo Cutillas MSc, at the laboratory of Professor Macarena Pern, PhD, University of Jan. Treatment with PRP was shown to have a favorable impact inhibiting, slowing, or reversing tumor development by acting as an anti-tumor agent, decreasing tumor cell proliferation, developing a non-malignant phenotype (observable characteristics) and promoting cell adhesion (sticking close to one another) and differentiation (cell specialization rather than stem cell like). It was concluded that PRP could have a significant impact on the tumor microenvironment as a potential clinical application. PRP is a combination of the two proenzymes trypsinogen and chymotrypsinogen.

Cancer remains one of the leading causes of death, globally. Despite recent advances in understanding its molecular and genetic basis, more than one third of those affected die each year from cancer. These alarming results are mainly attributed to current therapies not fully effective against cancer cells which may develop drug resistance, leading to recurrence and metastasis, causing more than 90% of cancer-related deaths. According to Mrs. Cutillas, This is why we need to find better and more effective therapeutic strategies. She explains that tumor formation is influenced by two factors, genetic changes in tumor cells and the rearrangement of components of the tumor microenvironment. In recent years, cancer research has focused on the tumor microenvironment.

Numerous assays, in vitro and in vivo studies, were conducted by Mrs. Cutillas confirming that PRP appears to have an anti-tumor effect and can act selectively against specific tumor elements, without affecting the non-tumor microenvironment and preventing its malignification (i.e., the process of making malignant).

Dr Julian Kenyon, MD, MB, ChB, Propancs Chief Scientific Officer said, The work undertaken by Mrs Cutillas highlights the significant potential applications of PRP in a clinical setting, specifically relating to drug resistance, and consequently recurrence and metastasis, which is the biggest cause of death for sufferers. The pioneering research being undertaken with our joint researchers at the Universities of Jan and Granada, continues to confirm our belief in the therapeutic potential of PRP, and may lead to exciting new ways to treat cancer patients suffering from solid tumors whilst reducing the threat of recurrence.

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

About Propanc Biopharma, Inc.

Propanc Biopharma, Inc. (the Company) is developing a novel approach to prevent recurrence and metastasis of solid tumors by using pancreatic proenzymes that target and eradicate cancer stem cells in patients suffering from pancreatic, ovarian and colorectal cancers. For more information, please visit http://www.propanc.com.

The Companys novel proenzyme therapy is based on the science that enzymes stimulate biological reactions in the body, especially enzymes secreted by the pancreas. These pancreatic enzymes could represent the bodys primary defense against cancer.

To view the Companys Mechanism of Action video on its anti-cancer lead product candidate, PRP, please click on the following link: http://www.propanc.com/news-media/video

Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are forward-looking statements, which may often, but not always, be identified by the use of such words as may, might, will, will likely result, would, should, estimate, plan, project, forecast, intend, expect, anticipate, believe, seek, continue, target or the negative of such terms or other similar expressions. These statements involve known and unknown risks, uncertainties and other factors, which may cause actual results, performance or achievements to differ materially from those expressed or implied by such statements. These factors include uncertainties as to the Companys ability to continue as a going concern absent new debt or equity financings; the Companys current reliance on substantial debt financing that it is unable to repay in cash; the Companys ability to successfully remediate material weaknesses in its internal controls; the Companys ability to reach research and development milestones as planned and within proposed budgets; the Companys ability to control costs; the Companys ability to obtain adequate new financing on reasonable terms; the Companys ability to successfully initiate and complete clinical trials and its ability to successful develop PRP, its lead product candidate; the Companys ability to obtain and maintain patent protection; the Companys ability to recruit employees and directors with accounting and finance expertise; the Companys dependence on third parties for services; the Companys dependence on key executives; the impact of government regulations, including FDA regulations; the impact of any future litigation; the availability of capital; changes in economic conditions, competition; and other risks, including, but not limited to, those described in the Companys periodic reports that are filed with the Securities and Exchange Commission and available on its website at http://www.sec.gov. These forward-looking statements speak only as of the date hereof and the Company disclaims any obligations to update these statements except as may be required by law.

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Propanc Biopharma Reports Significant Effects of PRP Against the Tumor Microenvironment - Business Wire

Skin Stem Cells Comments Off on Propanc Biopharma Reports Significant Effects of PRP Against the Tumor Microenvironment – Business Wire | September 11th, 2022

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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...

Bone Marrow Stem Cells Comments Off on Neuroplast receives second orphan medicinal product designation for Neuro-Cells, paving the way for application to both chronic and trauma-induced… | September 11th, 2022