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Stem cells in the brain: Limited self-renewal

By Stem Cell Treatment

The generation of neurons (neurogenesis) in humans is predominantly limited to development; in the adult stage it takes place in only a few regions of the brain. These regions contain neural stem cells that generate neurons in a process with various intermediary stages.

Stem cell renewal is limited - total number drops

Until now it was thought that maintaining the stem cell pool was based on the self-renewal of individual stem cells. The team of scientists headed by Dr. Jovica Ninkovic and Professor Dr. Magdalena Gtz were able to refute this: Both the self-renewal rate and the diversity of neurons formed from the stem cells are limited, and the number of stem cells decreases with age.

"Our findings explain why neurogenesis declines in later years, as there are fewer and fewer neural stem cells. At the same time, we gained new knowledge on basic mechanisms of neurogenesis that until now were not understood," says first author Dr. Filippo Calzolari.

Therapeutic approaches must focus on stem cells themselves

Approaches to new therapies for brain diseases, such as stroke or dementia, for example, particularly concentrate on replacing lost neurons by stimulating the generation of new cells from stem cells. "In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time," emphasizes Gtz, Director of the Institute for Stem Cell Research at the Helmholtz Zentrum Mnchen and Chair of the Institute of Physiological Genomics at LMU.

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Original publication:

Calzolari, F. et al. (2015). Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone. Nature Neuroscience, doi: 10.1038/nn.3963

Link to publication: http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.3963.html

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Stem cells in the brain: Limited self-renewal

Stem Cell Clones Could Yield New Drug Treatment for Deadly Blood Disease

By Stem Cell Treatment

Durham, NC (PRWEB) March 11, 2015

Scientists report in the current issue of STEM CELLS Translational Medicine that they have been able to clone a line of defective stem cells behind a rare, but devastating disease called Fanconi Anemia (FA). Their achievement opens the door to drug screening and the potential for a new, safe treatment for this often fatal disease.

FA is a hereditary blood disorder that leads to bone marrow failure (FA-BMF) and cancer. Patients who suffer from FA have a life expectancy of 33 years. Currently, a bone marrow transplant offers the only possibility for a cure. However, this treatment has many risks associated with it, especially for FA patients due to their extreme sensitivity to radiation and chemotherapy.

Although various consequences in hematopoietic stem cells (the cells that give rise to all the other blood cells) have been attributed to FA-BMF, its cause is still unknown, said Megumu K. Saito, M.D., Ph.D., of Kyoto Universitys Center for iPS Cell and Application, and a lead investigator on the study. His laboratory specializes in studying the kinds of pediatric diseases in which a thorough analysis using mouse models or cultured cell lines is not feasible, so they apply disease-specific induced pluripotent stem cells (iPSCs) instead.

To address the FA issue, he explained, our team (including colleagues from Tokai University School of Medicine) established iPSCs from two FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal type immature blood cells from these iPSCs.

When observing the iPSCs, the researchers found that the characteristics of immature blood cells from FA-iPSCs were different from control cells. The FA-iPSCs showed an increased DNA double-strand break rate, as well as a sharp reduction of hematopoietic stem cells compared to the control group of non-FA iPSCs.

These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs, said Dr. Saito. Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.

This work shows promise for identifying the initial pathological event that causes the disease, which would be a first step in working toward a cure, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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The full article, Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors, can be accessed at http://www.stemcellstm.com.

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Stem Cell Clones Could Yield New Drug Treatment for Deadly Blood Disease

Media portray unrealistic timelines for stem cell therapies

By Stem Cell Treatment

A new study by University of Alberta law researchers reveals sometimes overly optimistic news coverage of clinical translation of stem cell therapies--and as spokespeople, scientists need to be mindful of harnessing public expectations.

"As the dominant voice in respect to timelines for stem cell therapies, the scientists quoted in these stories need to be more aware of the importance of communicating realistic timelines to the press," said researcher Kalina Kamenova, who co-authored the study with professor Timothy Caulfield in the University of Alberta's Health Law Institute, based in the Faculty of Law.

Their analysis of media coverage showed that most news reports were highly optimistic about the future of stem cell therapies and forecasted unrealistic timelines for clinical use. The study, published in the latest issue of Science Translational Medicine, examined 307 news reports covering translational stem cell research in major daily newspapers in Canada, the United States and the United Kingdom between 2010 and 2013.

While the field of stem cell research holds tremendous promise, "it has also been surrounded by tremendous hype, and we wanted to quantify that in some degree," Caulfield said. "Pop culture representations have an impact on how the public perceives the readiness of stem cell research, and that in turn feeds into stem cell tourism, marketing of unproven therapies and even the public's trust in research. We wanted to provide findings that would help inform the issue."

Their study found that 69 per cent of all news stories citing timelines predicted that therapies would be available within five to 10 years or even sooner. At the same time, the press overlooked challenges and failures in therapy translation, such as the discontinuation of the first FDA-approved clinical trial of an embryonic stem cell-derived therapy for spinal cord injuries in 2011. The biotech company conducting the trial was a leader in embryonic stem cell therapies and its decision to stop its work on stem cells was considered a significant setback for the field.

As well, ethical concerns about the use of human embryonic stem cells were displaced from the forefront of news coverage, while the clinical translation of stem cell therapies and new discoveries, such as hockey star Gordie Howe's recent treatment, grabbed the headlines instead.

"Our findings showed that many scientists have often provided either by implication or direct quotes, authoritative statements regarding unrealistic timelines for stem cell therapies and media hype can foster unrealistic public expectations about clinical translation and increased patient demand for unproven stem cell therapies," Caulfield noted.

While stem cell therapy research is progressing and has seen a dramatic increase in the past decade of clinical trials for treatments, the vast majority of these studies are still in the safety-testing stage and involve a limited number of participants, Kamenova noted.

"The approval process for new treatments is long and complicated, and only a few of all drugs that enter pre-clinical testing are approved for human clinical trials. It takes on average 12 years to get a new drug from the lab to the market, and additional 11 to 14 years of post-market surveillance," she added.

The science world is under pressure to come up with cures for what ails us, but "care needs to be taken by the media and the research community so that advances in research and therapy are portrayed in a realistic manner," Caulfield said.

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Media portray unrealistic timelines for stem cell therapies

Building custom blood cells to battle sickle cell disease

By Uncategorized

March 10, 2015

These are human blood cells grown in the lab from genetically edited stem cells. (Credit: Ying Wang/Johns Hopkins Medicine)

Provided by Shawna Williams, Johns Hopkins Medicine

Researchers at Johns Hopkins have successfully corrected a genetic error in stem cells from patients with sickle cell disease, and then used those cells to grow mature red blood cells, they report. The study represents an important step toward more effectively treating certain patients with sickle cell disease who need frequent blood transfusions and currently have few options.

The results appear in an upcoming issue of the journalStem Cells.

In sickle cell disease, a genetic variant causes patients blood cells to take on a crescent, or sickle, shape, rather than the typical round shape. The crescent-shaped cells are sticky and can block blood flow through vessels, often causing great pain and fatigue. Getting a transplant of blood-making bone marrow can potentially cure the disease. But for patients who either cannot tolerate the transplant procedure, or whose transplants fail, the best option may be to receive regular blood transfusions from healthy donors with matched blood types.

[STORY: New injection helps stem traumatic blood loss]

The problem, says Linzhao Cheng, Ph.D. , the Edythe Harris Lucas and Clara Lucas Lynn Professor of Hematology and a member of the Institute for Cell Engineering, is that over time, patients bodies often begin to mount an immune response against the foreign blood. Their bodies quickly kill off the blood cells, so they have to get transfusions more and more frequently, he says.

A solution, Cheng and his colleagues thought, could be to grow blood cells in the lab that were matched to each patients own genetic material and thus could evade the immune system. His research group had already devised a way to use stem cells to make human blood cells. The problem for patients with sickle cell disease is that lab-grown stem cells with their genetic material would have the sickle cell defect.

To solve that problem, the researchers started with patients blood cells and reprogrammed them into so-called induced pluripotent stem cells, which can make any other cell in the body and grow indefinitely in the laboratory. They then used a relatively new genetic editing technique called CRISPR to snip out the sickle cell gene variant and replace it with the healthy version of the gene. The final step was to coax the stem cells to grow into mature blood cells. The edited stem cells generated blood cells just as efficiently as stem cells that hadnt been subjected to CRISPR, the researchers found.

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Building custom blood cells to battle sickle cell disease

Mother wins competition to have baby's stem cells frozen as an 'insurance policy'

By Stem Cell Doctors

Hannah Green's daughter Lola was born with congenital heart disease Mum from Gosport had blood from Lola's cord harvested at birth Her stem cells have been cryogenically frozen for 30 years

By Natalie Brown For Mailonline

Published: 02:42 EST, 2 March 2015 | Updated: 04:28 EST, 2 March 2015

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Hannah Green's 30th birthday is a day she will never forget but not for the reasons you might expect.

At 20 weeks pregnant, it was also the day Hannah, now 31, discovered her unborn daughter Lola had a congenital heart disease and would need open heart surgery as soon as she was born.

With no history of the condition in the family the unexpected news left Hannah and her partner Gerard Bradley, 30, from Gosport, Hampshire, devastated, and Hannah vowed to do everything she could to ensure her daughter had the best start in life.

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Mother wins competition to have baby's stem cells frozen as an 'insurance policy'

Johns Hopkins researchers engineer custom blood cells

By Uncategorized

IMAGE:These are human blood cells grown in the lab from genetically edited stem cells. view more

Credit: Ying Wang/Johns Hopkins Medicine

Researchers at Johns Hopkins have successfully corrected a genetic error in stem cells from patients with sickle cell disease, and then used those cells to grow mature red blood cells, they report. The study represents an important step toward more effectively treating certain patients with sickle cell disease who need frequent blood transfusions and currently have few options.

The results appear in an upcoming issue of the journal Stem Cells.

In sickle cell disease, a genetic variant causes patients' blood cells to take on a crescent, or sickle, shape, rather than the typical round shape. The crescent-shaped cells are sticky and can block blood flow through vessels, often causing great pain and fatigue. Getting a transplant of blood-making bone marrow can potentially cure the disease. But for patients who either cannot tolerate the transplant procedure, or whose transplants fail, the best option may be to receive regular blood transfusions from healthy donors with matched blood types.

The problem, says Linzhao Cheng, Ph.D. , the Edythe Harris Lucas and Clara Lucas Lynn Professor of Hematology and a member of the Institute for Cell Engineering, is that over time, patients' bodies often begin to mount an immune response against the foreign blood. "Their bodies quickly kill off the blood cells, so they have to get transfusions more and more frequently," he says.

A solution, Cheng and his colleagues thought, could be to grow blood cells in the lab that were matched to each patient's own genetic material and thus could evade the immune system. His research group had already devised a way to use stem cells to make human blood cells. The problem for patients with sickle cell disease is that lab-grown stem cells with their genetic material would have the sickle cell defect.

To solve that problem, the researchers started with patients' blood cells and reprogrammed them into so-called induced pluripotent stem cells, which can make any other cell in the body and grow indefinitely in the laboratory. They then used a relatively new genetic editing technique called CRISPR to snip out the sickle cell gene variant and replace it with the healthy version of the gene. The final step was to coax the stem cells to grow into mature blood cells. The edited stem cells generated blood cells just as efficiently as stem cells that hadn't been subjected to CRISPR, the researchers found.

Cheng notes that to become medically useful, the technique of growing blood cells from stem cells will have to be made even more efficient and scaled up significantly. The lab-grown stem cells would also need to be tested for safety. But, he says, "This study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option."

This method of generating custom blood cells may also be applicable for other blood disorders, but its potential does not end there, Cheng says. One possibility, which his group hopes to begin studying soon, is that the blood cells of healthy people could be edited to resist malaria and other infectious agents.

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Johns Hopkins researchers engineer custom blood cells

Targazyme Inc. Receives Orphan Drug Designation to TZ101 for Use With Regulatory T Cells to Prevent & Reduce the …

By Uncategorized

Orphan Designation Provides 7-Year Post Approval Marketing Exclusivity, Tax Credits and Elimination of FDA Prescription Drug User Fees

SAN DIEGO, CA--(Marketwired - February 10, 2015) - Targazyme Inc., a clinical-stage biopharmaceutical company developing enzyme technologies and products to improve efficacy outcomes for stem cell transplantation, immunotherapy, gene therapy and regenerative medicine, announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to TZ101 to prevent and reduce the severity and incidence of graft vs. host disease (GVHD) in patients eligible for hematologic stem cell transplant.

GVHD is a serious, life-threating complication of stem cell transplantation.Orphan drug status confirms the importance of Targazyme's novel treatment approach to prevent and reduce the incidence and severity of GVHD in patients with blood cancers where stem cell transplant is prescribed.TZ101 could potentially transform hematopoietic stem cell transplantation by reducing patient morbidity and mortality from GVHD, which occurs in a large percentage of these patients and is very difficult to manage clinically.

"Our work with TZ101 demonstrates impressive increases in the persistence and activity of regulatory T cells in preclinical models of GVHD," said Dr. Elizabeth J. Shpall, Deputy Chair of the Department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center."We are looking forward to beginning clinical trials on this promising modality for preventing GVHD in our patients undergoing stem cell transplantation."

Orphan Drug Designation by FDA confers financial benefits and incentives, such as potential Orphan Drug grant funding to defray the cost of clinical testing, tax credits for the cost of clinical research, a 7 year period of exclusive marketing after Approval and a Waiver of Prescription Drug User Fee Act (PDUFA) filing fees which are now greater than $2 million.

"The granting of Orphan Drug status for TZ101 for prevention of GVHD in stem cell transplant patients, as well as our previous Orphan Drug designation of TZ101 for cord blood transplantation, provides additional validation of our innovative platform technologies," said Lynnet Koh, Chairman & Chief Executive Officer of Targazyme."TZ101 and our second product, TZ102 are enabling technologies for improving efficacy outcomes for multiple cell-based therapeutic approaches used to prevent and treat a variety of different diseases for which there is a high unmet medical need.In addition to initiating our registration trial with TZ101 in hematopoietic stem cell transplantation, we plan to embark on our cancer immunotherapy trial later this year."

About Targazyme, Inc.

Targazyme Inc. is a San Diego-based, clinical-stage biopharmaceutical company developing novel enzyme-based platform technologies and products to improve clinical efficacy outcomes for stem cell medicine, auto-immunotherapy, gene therapy and regenerative medicine.

The company's clinical-grade fucosyltransferase enzymes and small molecule products (TZ101 and TZ102) are off-the-shelf products used at the point-of-care to treat therapeutic cells immediately before infusion into the patient using a simple procedure that is easily incorporated into existing medical practice.The company has received a number of world-wide patents, multiple FDA orphan drug designations and major medical/scientific awards and grants.

Targazyme has partnerships and collaborations with Kyowa Hakko Kirin and Florida Biologix, as well as various medical research institutions including The University of Texas MD Anderson Cancer Center, Oklahoma Medical Research Foundation, Texas Transplant Institute, Case Western/University Hospitals, Scripps Hospitals, Fred Hutchinson Cancer Research Center, UCLA Medical Center, Stanford University Medical Center, University of Minnesota Medical Center, University of California San Diego, Sanford-Burnham Medical Research Institute, Indiana University, Memorial Sloan Kettering Cancer Center, and New York Blood Center.For more information please go to http://www.targazyme.com.

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Targazyme Inc. Receives Orphan Drug Designation to TZ101 for Use With Regulatory T Cells to Prevent & Reduce the ...

Girl meets Austrian stem cell donor who helped her beat cancer

By Stem Cell Treatment

Sabrina Chahir was waiting to meet the man who helped send her cancer into remission.

The 8-year-old from Mount Prospect, who likes art and takes piano lessons, knew he had flown across an ocean to see her, nearly four years after he donated his stem cells to help rid her blood of cancer that could have taken her life.

Thursday evening, Sabrina and Maximilian Eule, 30, had their first face-to-face meeting at a celebration in Schaumburg with Sabrina's friends and family.

The two had emailed and video-chatted. But Sabrina's mother, Natalia Wehr, said it was important to her to meet Eule in person.

"It's your daughter, and this person we don't know did something so wonderful," Wehr said. "You need to know who that is."

Sabrina was diagnosed with acute lymphoblastic leukemia, one of the most common types of cancer in children, when she was 2 1/2. The cancer cells were in more than 80 percent of her blood.

The girl's cancer had gone into remission before, but she soon relapsed. After rounds of treatment and infections that caused Sabrina to go blind temporarily, doctors at Lurie Children's Hospital of Chicago told Sabrina's family she would need a stem cell transplant.

"It was the most painful thing you can imagine," Wehr said. "Not knowing if your child is going to live or not. It's the worst feeling in the world."

Ten to 15 percent of children diagnosed with this type of leukemia need a stem cell transplant, but the treatment is more common for other types of cancer, said Dr. Reggie Duerst, one of Sabrina's doctors and director of the stem cell transplant program at Lurie.

And while doctors said the best donor matches are often people of similar racial and ethnic backgrounds Sabrina is Hispanic and Arab her match, located through a computer database, turned out to be a German man who lives in Austria.

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Girl meets Austrian stem cell donor who helped her beat cancer

Deadly shortage of black stem cell donors

By Stem Cell Doctors

Black South Africans make up about 47 percent of all cancer patients but only 5 percent of donors in the nations bone marrow registry. The gap between those who may need bone marrow or stem cell transplants, and those able to provide them has deadly consequences for cancer patients.

Black South Africans make up about 47 percent of all cancer patients but only 5 percent of donors in the nations bone marrow registry

Maphoko Nthane, 50, had experienced mysterious and severe backaches for months. Doctors ran test after test, but could find nothing wrong with Nthane.

I had a severe back ache for months, she told Health-e News. Whenever I would have that pain, I couldnt sit down I had to walk or stand up.

Doctors eventually diagnosed Nthane with Acute Lymphoblastic Leukaemia, a severe form of cancer affecting a patients blood and bone marrow.

After I was diagnosed I thought I was going to die I didnt know that people with leukaemia could live, Nthane said. My husband was just as traumatised and as a result he didnt know how to support me.

Nthanes cancer failed to respond to standard chemotherapy and ultimately a stem cell transplant saved her life.

As part of stem cell transplants, stem cells are removed from the tissue of donors or, where possible, patients. These cells are usually from human tissues including bone marrow or fat.

Once removed, the stem cells are given high doses of chemotherapy higher than what could be administered to patients before being transplanted into patients in the hope that they will kill other cancerous cells.

Nthane was lucky to find a stem cell donor.

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Deadly shortage of black stem cell donors

Twin copies of gene pair up in embryonic stem cells at critical moment in differentiation

By Stem Cell Medicine

Both copies of the Oct4 gene physically come together just as embryonic stem cells begin to develop into tissue-specific cell types

IMAGE:We and other mammals have two copies of each gene, and each copy, or 'allele,' was thought to remain physically apart from the other in the cell nucleus. David Spector's... view more

Credit: Spector Lab, CSHL

Cold Spring Harbor, NY -- Imagine a pair of twins that everyone believed to be estranged, who turn out to be closer than anyone knew. A genetic version of this heartwarming tale might be taking place in our cells. We and other mammals have two copies of each gene, one from each parent. Each copy, or "allele," was thought to remain physically apart from the other in the cell nucleus, but a new study finds that alleles can and do pair up in mammalian cells.

Intriguingly, the pairing of at least one set of alleles has been observed to coincide with a critical time in the life of a stem cell: the moment when it commits to develop into a specific cell type. This process is called differentiation.

In work published today in Cell Stem Cell a team of researchers led by Professor David L. Spector at Cold Spring Harbor Laboratory (CSHL) showed that the two alleles of Oct4, a gene important in embryonic stem cells, did not come together randomly, at any time or place, but did so at the developmental point at which stem cells begin their maturation into specific cell types.

Spector, along with Megan Hogan, Ph.D., lead author on the new paper, and colleagues, began by observing the location within the cell nucleus of various genes known to be important in stem cells. "We examined hundreds of cells, and we made the interesting and unexpected finding that the two alleles of the Oct4 gene tended to co-localize together in about 25% of the cells," Spector says. "This was really unexpected, but it's the sort of image that's worth a thousand words."

Examining enough single cells to make sure the team was observing a widespread phenomenon was no easy task. "It was a lot of work, but I think in the end the pictures that come out of it, the stories that we have gotten out if it, makes it worth it," says Hogan, a recent doctoral student in the Spector Lab and now a postdoctoral investigator at the Icahn School of Medicine at Mount Sinai.

To figure out if what they were seeing was physiologically important, the team studied whether they could manipulate the timing of the Oct4 pairing during differentiation. They used different methods to cause the stem cells to differentiate, and found that the more rapidly the cells differentiated, the earlier Oct4 pairing occurred. "This supported the notion that this was a potentially very exciting finding," Spector says.

To confirm that the Oct4 pairing wasn't something that only occurred in tissue culture, the team then looked in mouse embryos. "The pairing was equal to or even a little bit more frequent than in culture, and that was really comforting and extremely convincing to us that there is physiological relevance to this," Spector says.

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Twin copies of gene pair up in embryonic stem cells at critical moment in differentiation

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