Stem Cell Clinic

Stem cells: Hope on the line : Nature News & Comment

By Stell Cell Research

On a brilliant day in April, tens of thousands of baseball fans stream past Jonathan Thomas's office towards AT&T Park for the first home game of the San Francisco Giants 2014 season. Thomas's standing desk faces away from the window, but the cheering throngs are never far from his mind.

Thomas chairs the board of the California Institute for Regenerative Medicine (CIRM), the US$3-billion agency hailed by scientists around the world for setting a benchmark for stem-cell research funding. But scientists will not be the ones who decide what becomes of CIRM when the cash runs out in 2017. Instead, it will be the orange-and-black-clad masses walking past Thomas's window. And to win their support, Thomas knows that the agency needs to prove that their collective investment has been worthwhile. We need to drive as many projects to the patient as soon as possible, he says.

Californians voted CIRM into existence in 2004, making it the largest funder of stem-cell work in the world. The money the proceeds of bond sales that must be repaid with $3 billion in interest by taxpayers helped to bring 130 scientists to the state, and created several thousand jobs there. It has funded research that led to the publication of more than 1,700 papers, and it has contributed to five early clinical trials.

The institute has navigated a difficult path, however. CIRM had to revamp its structure and practices in response to complaints about inefficiency and potential conflicts of interest. It has also had to adapt its mission to seismic shifts in stem-cell science.

Now, ten years after taking off, the agency is fighting for its future. It has a new president, businessman Randal Mills, who replaces biologist Alan Trounson. Its backers have begun to chart a course for once again reaching out to voters, this time for $5 billion (with another $5 billion in interest) in 2016. And it is under intense pressure to produce results that truly matter to the public.

Whether or not CIRM succeeds, it will serve as a test bed for innovative approaches to funding. It could be a model for moving technologies to patients when conventional funding sources are not interested.

Much of what is celebrated and lamented about CIRM can be traced back to the Palo Alto real-estate developer who conceived of it: Robert Klein. Although officially retired from CIRM he chaired the board from 2004 to 2011 (see 'State of funding') Klein's office is adorned with mementos of the agency: a commemorative shovel from the groundbreaking of a CIRM-funded stem-cell research centre, and a photo of him with former governor Arnold Schwarzenegger at the ribbon-cutting ceremony.

Liz Hafalia/San Francisco Chronicle/Polaris/eyevine

Patient advocates and parents at a 2012 meeting in which US$100 million in CIRM grants were approved.

It was Klein's idea to ask voters to support stem-cell research in 2004, through a ballot measure called Proposition 71. When he succeeded, CIRM instilled a kind of euphoria in stem-cell scientists, who were at the time still reeling from a 2001 decree by then-President George W. Bush that severely limited federal funding for embryonic-stem-cell research. California's commitment removed this roadblock and revealed that many in the state and the country supported the research.

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Stem cells: Hope on the line : Nature News & Comment

Scientists Withdraw Report on Simpler Stem Cells – ABC News

By Stell Cell Research

U.S. and Japanese scientists who reported that they'd found a startlingly simple way to make stem cells withdrew that claim Wednesday, admitting to "extensive" errors in the research.

In two papers published in January in the journal Nature, the researchers said that they'd been able to transform ordinary mouse cells into versatile stem cells by exposing them to a mildly acidic environment. Someday, scientists hope to harness stem cells to grow replacement tissue for treating a variety of diseases.

While researchers have long been able to perform such transformations with a different method, the newly reported technique was far simpler, and the papers caused a sensation and some skepticism in the research community. They were also widely reported in the media, including by The Associated Press.

But before long, the government-funded Riken Center for Developmental Biology in Japan accused one of its scientists, Haruko Obokata, of falsifying data in the research. Obokata, the key author of the papers, defended the results during a televised news conference in April while apologizing for using wrong and altered images in the published reports. She also said she opposed withdrawing the papers, a process called retraction, and the 30-year-old attributed her mistakes to inexperience.

On Wednesday, Nature released a statement from Obokata and the other authors of the papers that retracted the papers, a rare occurrence for the prestigious journal. The scientists acknowledged "extensive" errors that meant "we are unable to say without a doubt" that the method works. They noted that studies of the simpler method are still going on by other researchers.

The Riken center also said on its website Wednesday that it expected a separate statement from Obokata and would post it when available.

Dr. Charles Vacanti of the Harvard-affiliated Brigham and Women's Hospital in Boston, another main author, issued his own statement in which he said he believes the further studies will vindicate the method, which produced what the authors called STAP cells.

But another author, Yoshiki Sasai, deputy director of the Riken center, said the errors in the papers meant "it has become increasingly difficult to call the STAP phenomenon even a promising hypothesis." In a statement issued by Riken, he said he was "deeply ashamed" of the problems in the papers.

The Riken investigation that led to allegations against Obokata also focused on Sasai and two other employees, but they were not accused of research misconduct.

Retractions of papers in major scientific journals like Nature are unusual. They can come about because of fraud or the discovery of honest mistakes that undercut the conclusions of research. Publications like Nature routinely have experts review papers submitted by scientists to look for problems. But in an editorial released Wednesday, Nature concluded that its editors and reviewers "could not have detected the fatal faults in this work."

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Scientists Withdraw Report on Simpler Stem Cells - ABC News

Bone marrow transplants can reverse adult sickle cell disease

By Stem Cell Doctors

This image provided by the National Institutes of Health shows red blood cells in a patient with sickle cell disease at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

This image provided by the National Institutes of Health shows red blood cells in a different sickle cell patient, after a bone marrow transplant at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results seen with a similar technique used in children.

The researchers and others say the findings show age need not be a barrier and that the technique may change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were even able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening; patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, with hopes that the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

Originally posted here:
Bone marrow transplants can reverse adult sickle cell disease

Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Krysten Carrera NIDDKMedia@mail.nih.gov 301-496-3583 NIH/National Institute of Diabetes and Digestive and Kidney Diseases

Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health's Clinical Center in Bethesda, Maryland, by researchers from NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.

The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.

"Typically, stem-cell recipients must take immunosuppressants all their lives," said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. "That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen."

In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard "full" transplant, which uses high doses of chemotherapy to kill all of the patient's marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.

Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.

"Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease," said John F. Tisdale, M.D., the paper's senior author and a senior investigator at NIH. "Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition."

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Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease

Papers on stress-induced stem cells are retracted

By Stem Cell Medical Center

Asahi Shimbun/Getty Images

Haruko Obokata, here at a 9 April news conference in Osaka, Japan, was found guilty of misconduct but stands by her claim of having produced stem cells by a novel procedure.

Nature today retracted two controversial papers on stem cells that it published in January1, 2. The retractions agreed to by all of the co-authors come at the end of a whirlwind five months during which various errors were spotted in the papers, attempts to replicate the experiments failed, the lead author was found guilty of misconduct, and the centre where she is employed was threatened with dismantlement. The retraction notice3 includes a handful of problems with the papers that had not been previously considered by institutional investigation teams.

Questions remain over what exactly was the basis for claims that embryonic-like stem cells could be created by exposing bodily cells to stress a technology the authors called stimulus-triggered acquisition of pluripotency, or STAP. But the controversy promises to have lasting impact on science in Japan, global stem-cell research, and the scientific community more broadly including changes in editorial policy at Nature. An Editorial posted today with the retractions notes the need for improvements in publishing procedures: The episode has further highlighted flaws in Natures procedures and in the procedures of institutions that publish with us. (Natures news and comment team is editorially independent of its research editorial team.)

The first of the two papers1 described a method of using acid exposure or physical pressure to convert spleen cells from newborn mice into pluripotent cells cells that can become any cell in the body. The second paper2 further impressed stem-cell scientists with data showing that the STAP process created cells that could differentiate into placenta cells, something that other pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, do not normally do.

But within weeks, duplicated and manipulated images were discovered, focusing attention on the source of data provided by Haruko Obokata, a biochemist at the RIKEN Center for Developmental Biology in Kobe and first author on both papers. Scientists also reported difficulties in replicating the experiments.

A RIKEN investigation team looking into the papers announced on 1 April that Obokata had been found guilty of two counts of scientific misconduct. RIKEN rejected an appeal, and advised her to retract the papers in May. Co-author Teruhiko Wakayama of the University of Yamanishi had been arguing for retraction since March.

Obokata and Charles Vacanti, an anaesthesiologist at the Brigham and Womens Hospital in Boston, Massachusetts, and the senior corresponding author on the first article, both stood by its claims, but later changed their positions after new errors emerged. Obokata gave her consent to the retraction of both papers on 4 June.

The retraction notice published today lists five new errors. The first four note that captions do not describe what is in the corresponding images or figures, without reflecting on how this relates to the experimental data. The fifth, relating to the first paper1, notes that purported STAP cells are of a different genetic background from those supposedly used in the experiments something it calls inexplicable discrepancies.

The notice concludes: These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC [stem cell] phenomenon is real.

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Papers on stress-induced stem cells are retracted

Acid-bath stem cell papers are finally retracted

By Uncategorized

The STAP stem cell saga has reached its bitter conclusion for now.

The authors of two papers published by the journal Nature, which claimed to have produced embryonic-like stem cells from adult cells, have retracted them.

The papers said that almost any adult cell could be coaxed into becoming a stem cell just by dipping them in a bath of acid for 30 minutes. The method held great promise for regenerative medicine because it could be used to create any cell without needing to reprogram genes, or destroy an embryo. The team, led by researchers at the Riken Institute in Kobe, Japan, called this technique stimulustriggered acquisition of pluripotency, or STAP.

But in the months after publication, no independent team was able to replicate the experiments. Instead, the researchers around the world scrutinising the papers exposed many flaws in the papers including manipulated pictures of protein gel panels and mislabelled images. A public flogging of many high profile researchers ensued (see ""How the STAP cell story unfolded", below) and Nature's review process was thrust into the spotlight.

The journal published two statements today from the authors saying they were retracting both papers. The statements include an apology from the authors, in which they admit that multiple errors impair the credibility of the study. They concede that they are unable to say without doubt whether the STAP cell phenomenon is real.

An accompanying Nature editorial says that in practice, it may be impossible for journals to police gel panels routinely "without disproportionate editorial effort". The journal says it is now reviewing its screening practices to increase such checks.

The editorial goes on to say that Nature believes that its editors and referees could not have detected the fatal faults in this work. However, it emerged during the investigation that the papers were first submitted for publication in Science. According to a Nature News blog, Science rejected them after spotting the manipulated images and warning the lead author of the papers, Haruko Obokata, that such composite images need to be marked. Soon after the papers were published, independent bloggers started finding discrepancies in the work.

The Nature editorial states that the episode has highlighted flaws in Nature's procedures. The journal says that it needs to put quality assurance even higher on its agenda to make sure that people's trust in science is not betrayed.

Charles Vacanti at Harvard Medical School, one of the authors on the papers, has said that he is deeply saddened by the whole episode, although he continues to believe that none of the issues cast doubt on the existence of STAP cells themselves. He says he is encouraged that Riken president Ryoji Noyori and other independent labs will now allow sufficient time to try to replicate the experiments.

29 January Two high profile papers are published in Nature claiming that adult cells could be coaxed into becoming stem cells by dipping them in a bath of acid for 30 minutes. The team call these new cells stimulustriggered acquisition of stem cells, or STAP cells.

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Acid-bath stem cell papers are finally retracted

Stem cells: Hope on the line

By Uncategorized

On a brilliant day in April, tens of thousands of baseball fans stream past Jonathan Thomas's office towards AT&T Park for the first home game of the San Francisco Giants 2014 season. Thomas's standing desk faces away from the window, but the cheering throngs are never far from his mind.

Thomas chairs the board of the California Institute for Regenerative Medicine (CIRM), the US$3-billion agency hailed by scientists around the world for setting a benchmark for stem-cell research funding. But scientists will not be the ones who decide what becomes of CIRM when the cash runs out in 2017. Instead, it will be the orange-and-black-clad masses walking past Thomas's window. And to win their support, Thomas knows that the agency needs to prove that their collective investment has been worthwhile. We need to drive as many projects to the patient as soon as possible, he says.

Californians voted CIRM into existence in 2004, making it the largest funder of stem-cell work in the world. The money the proceeds of bond sales that must be repaid with $3 billion in interest by taxpayers helped to bring 130 scientists to the state, and created several thousand jobs there. It has funded research that led to the publication of more than 1,700 papers, and it has contributed to five early clinical trials.

The institute has navigated a difficult path, however. CIRM had to revamp its structure and practices in response to complaints about inefficiency and potential conflicts of interest. It has also had to adapt its mission to seismic shifts in stem-cell science.

Now, ten years after taking off, the agency is fighting for its future. It has a new president, businessman Randal Mills, who replaces biologist Alan Trounson. Its backers have begun to chart a course for once again reaching out to voters, this time for $5 billion (with another $5 billion in interest) in 2016. And it is under intense pressure to produce results that truly matter to the public.

Whether or not CIRM succeeds, it will serve as a test bed for innovative approaches to funding. It could be a model for moving technologies to patients when conventional funding sources are not interested.

Much of what is celebrated and lamented about CIRM can be traced back to the Palo Alto real-estate developer who conceived of it: Robert Klein. Although officially retired from CIRM he chaired the board from 2004 to 2011 (see 'State of funding') Klein's office is adorned with mementos of the agency: a commemorative shovel from the groundbreaking of a CIRM-funded stem-cell research centre, and a photo of him with former governor Arnold Schwarzenegger at the ribbon-cutting ceremony.

Liz Hafalia/San Francisco Chronicle/Polaris/eyevine

Patient advocates and parents at a 2012 meeting in which US$100 million in CIRM grants were approved.

It was Klein's idea to ask voters to support stem-cell research in 2004, through a ballot measure called Proposition 71. When he succeeded, CIRM instilled a kind of euphoria in stem-cell scientists, who were at the time still reeling from a 2001 decree by then-President George W. Bush that severely limited federal funding for embryonic-stem-cell research. California's commitment removed this roadblock and revealed that many in the state and the country supported the research.

Excerpt from:
Stem cells: Hope on the line

News Review From Harvard Medical School — Transplant May Help Adults with Sickle Cell

By Stem Cell Treatment

July 2, 2014

News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

A partial transplant of bone-marrow stem cells may reverse sickle cell disease in adults, a new study finds. People with sickle cell disease have abnormally shaped red blood cells. They get stuck in blood vessels. This causes organ damage, pain and other medical problems. The new study included 30 adults with severe sickle cell disease. Each of them had a brother or sister who was a suitable match for a bone-marrow stem cell transplant. The sibling donor's cells were mixed with some of the patient's own cells. During 3.4 years of follow-up, the partial transplant reversed sickle cell disease in 26 out of 30 people, researchers said. In these patients, the bone marrow began making normal red blood cells. Fifteen people also were able to stop taking drugs to prevent rejection of the transplant. Overall, people were much less likely than before to need hospital treatment for the disease. Use of narcotic drugs for pain also was greatly reduced. The Journal of the American Medical Association published the study. HealthDay News wrote about it July 1.

By Howard LeWine, M.D.Harvard Medical School

What Is the Doctor's Reaction?

In the United States, more than 90,000 people are affected by sickle cell disease. Most of them are African-American. Worldwide, the number is much higher. About 300,000 babies are born with this genetic disease every year.

In sickle cell disease, the red blood cells made in the bone marrow are abnormal. Instead of having a normal round shape, the cells are curved and stiff. This causes the red blood cells to get stuck inside blood vessels before they reach the tissues. The result:

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News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

Marrow transplants can reverse adult sickle cell

By Stem Cell Treatment

CHICAGO (AP) Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results seen with a similar technique used in children.

The researchers and others say the findings show age need not be a barrier and that the technique may change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were even able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening; patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, with hopes that the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

Sickle cell disease is a genetic condition that damages oxygen-carrying hemoglobin in red blood cells, causing them to form abnormal, sickle shapes that can block blood flow through the veins. It can cause anemia, pain and organ damage. The disease affects about 100,000 Americans, mostly blacks, and millions worldwide.

Results from the adult study, involving patients aged 29 on average, were published Tuesday in the Journal of the American Medical Association. The usual treatment hadn't worked, a drug called hydroxyurea, and they had transplants at an NIH research hospital in Bethesda, Maryland.

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Marrow transplants can reverse adult sickle cell

UVA Expands Cancer Treatment

By Stem Cell Medical Center

UVA joins National Marrow Donor Program giving greater access to cancer treatments by Ishaan Sachdeva | Jun 25 2014 | 06/25/14 10:11pm | Updated 19 hours ago

The Emily Couric Cancer Center of the University of Virginia Health System has expanded its access to bone marrow and hematopoietic stem cell transplant donors. Now designated as a National Marrow Donor Program (NMDP), the Health System will have access to the Be The Match Registry, the worlds largest and most diverse bone marrow registry. Implications of this change are significant for patients afflicted with blood cancers like leukemia who obtain treatment through the Health System.

Bone marrow, the soft, spongy tissue within bones like the sternum or the ilium of the pelvis, forms hematopoietic or blood-forming stem cells. These cells, unlike embryonic stem cells, differentiate only into types of blood cells- red blood cells, white blood cells or clotting platelets. Leukemia causes bone marrow to produce abnormal, leukemic white blood cells that divide uncontrollably, forming tumors that deprive cells of oxygen and reduce infection defense. One treatment method is autologous bone marrow transplant, in which patients receive stem cells from their healthy, non cancerous bone marrow.

The idea [of autologous transplants] is that you extract healthier bone marrow from the patient to have a source of stored, non-cancerous bone marrow. You can then treat the patient with higher doses of treatment than you can normally give because the most common limitation to treatment is that treatment will kill off healthy bone marrow you might have, said Thomas P. Loughran Jr., MD, the Universitys Cancer Center director.

Essentially, a patients healthy bone marrow is safeguarded outside their body while aggressive treatment is administered to kill cancerous marrow. Another form of treatment is allogeneic treatment, in which bone marrow is transplanted from a sibling or an unrelated donor.

In an allogeneic transplant, you are also transplanting in a new immune system. The new immune system comes in and recognizes the body as a foreign tissue and starts attacking that tissue. This causes a beneficial graft vs. leukemia effect where this new immune system attacks any residual leukemia, but may also cause a harmful graft versus host disease where normal tissue is also attacked, Loughran said.

The donor and recipient tissue interaction underscores the genetic component of bone marrow transplants from external donors. Despite the curative potential of a bone marrow transplant, a strong genetic match between donor and recipient is crucial to the utility of a transplant.

The ability of any donor to be successful is based on genetics. Its called HLA [human leukocyte antigen] typing. The HLA system has four genes called A, B, C and D, and it turns out that A, B and D are influential. We have half of our genes each from both parents, so we have six of these: 2 A, 2 B and 2 D. The best case is a six out of six match from a brother or sister, but the chances are only 1 in 4, said Loughran. The consequence of low genetic probabilities is a large pool of unrelated donors, like the Be The Match Registry. Through such services, patients have a greater chance of finding an unrelated donor who may provide a successful genetic match.

The coordinating center would identify the place where the donor is living and tell them they are potentially able to donate. In the past, the donor would have bone marrow directly extracted. Now it is almost always from the PBSCT [peripheral blood stem cell transplantation] procedure. The donor takes a growth factor that stimulates growth of the needed hematopoietic stem cells within their peripheral blood circulation. A catheter collects this blood and the stem cells are separated from the blood by a machine, and the blood is returned back to the donor. The collected stem cells are sent to the lab where they are purified and frozen, Loughran said.

Meanwhile, the patient in preparation for the transplant is given the highest dose of chemotherapy that can be tolerated. The donated stem cells are administered to the patient in a way similar to IV fluid.

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UVA Expands Cancer Treatment

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