TIME medicine

This New Kind of Stem Cell May Revolutionize How We Treat Diseases

Scientists have created a new type of stem cell that could speed treatments for diseases and make them safer

Ever since Japanese researcher Shinya Yamanaka found a way to treat skin cells with four genes and reprogram them back to their embryonic state, scientists have been buzzing over the promise of stem cell therapies. Stem cells can be coaxed to become any of the body’s cell types, so they could potentially replace diseased or missing cells in conditions such as diabetes or Alzheimer’s. And Yamanaka’s method also meant that these cells could be made from patients themselves, so they wouldn’t trigger dangerous immune rejections.

Now scientists led by Dr. Andras Nagy at Mount Sinai Hospital Lunenfeld-Tanenbaum Research Institute in Toronto report an exciting new advance that could push stem cells even closer to the clinic. In a series of papers in the journals Nature and Nature Communications, the group describes a new class of stem cell, which they called F class, that they generated in the lab.

The F class cells, says Nagy, have a few advantages over the Yamanaka-generated induced pluripotent stem cells, or iPS cells. While the iPS cells are created by using viruses to introduce four genes that reprogram the cells, Nagy’s team relied on a technique they developed several years ago using transposons—small pieces of DNA that can insert themselves into different parts of a genome. Unlike viruses, these transposons can be popped out of the genome if they’re no longer needed, and they don’t carry the potential risk of viral infection.

MORE: Stem-Cell Research: The Quest Resumes

Nagy’s team found that the transposons were much more reliable vehicles for delivering the reprogramming genes exactly where they were needed to efficiently turn the clock back on the skin cells. What’s more, they could use the common antibiotic doxycycline to turn the four genes on and off; adding doxycycline to the cell culture would trigger the transposons to activate, thus turning on the genes, while removing the antibiotic would turn them off.

In this way, says Nagy, he was able to pump up the efficiency of the reprogramming process. Using the Yamanaka method, it was hit-or-miss whether the viruses would find their proper place in a cell’s genome, and more uncertainty over how effectively it could direct the cell to activate the four reprogramming genes. “F class cells are much more similar [in the culture dish], like monozygotic twins while iPS cells are more like brothers and sisters,” he says.

That consistency is a potential advantage of the transposon method, since any stem cell-based treatment would require a robust population of stem cells which can then be treated with the proper compounds to develop into insulin-making pancreatic cells to treat diabetes, or new nerve cells to replace dying ones in Alzheimer’s, or fresh heart muscle to substitute for scarred tissue after a heart attack.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimer’s

Nagy’s team also described, with the most detail to date, exactly how mature cells like skin cells perform the ultimate molecular feat and become forever young again when exposed to the four genes. They analyzed the changes in the cells’ DNA, the proteins they made, and more. “It’s similar to high definition TV,” he says. “We see things much better with much more detail. We expect that having that high resolution characterization will allow us to better understand what is happening during this process at the molecular level. And obviously that better understanding is going to affect what we can do with these cells to make them better, safer and more efficient in cell-based treatments in the future.”

That may be years away yet, especially since some experts say that transposons may pose their own risk of wreaking DNA havoc on a cell’s genome. But having another type of stem cell that could potentially churn out healthy cells and tissues to replaced diseased ones is a welcome development.

TIME medicine

‘Bubble Boy’ Disease Cured With Stem Cells

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life.
Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. Courtesy of UCLA

Researchers have treated more than two dozen patients with a treatment made from their own bone marrow cells

Alysia Padilla-Vaccaro and Christian Vaccaro owe their daughter’s life to stem cells. Evangelina, now two, is alive today because she saved herself with her own bone marrow cells.

Evangelina, a twin, was born with a severe immune disorder caused by a genetic aberration that makes her vulnerable to any and all bacteria and viruses; even a simple cold could be fatal. But doctors at University of California Los Angeles (UCLA) Broad Stem Cell Research Center gave her a new treatment, using her own stem cells, that has essentially cured her disease. She’s one of 18 children who have been treated with the cutting-edge therapy, and the study’s leader, Dr. Donald Kohn, says that the strategy could also be used to treat other gene-based disorders such as sickle cell anemia.

Known to doctors as adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), it’s better known as “bubble boy” disease, since children born with the genetic disorder have immune systems so weak that they need to stay in relatively clean and germ-free environments. Until Evangelina and her sister Annabella were 11 months old, “We were gowned and masked and did not go outside,” says their mother Alysia Padilla-Vaccaro. “Our children did not physically see our mouths until then because we were masked all the time. We couldn’t take them outside to take a breath of fresh air, because there is fungus in the air, and that could kill her.”

Both parents wore masks at work to lower the chances they would be exposed to germs that they might bring back home. And they took showers and changed clothes as soon as they entered the house.

MORE: Gene-Therapy Trial Shows Promise Fighting ‘Bubble Boy’ Syndrome

SCID is caused by a genetic mutation in the ADA gene, which normally produces the white blood cells that are the front lines of the body’s defense against bacteria and viruses. The Vaccaros decided to treat Annabella in the same way that they cared for Evangelina; “They were crawling and playing with each other, and every toy they sucked on, they stuck in each other’s hands and each other’s mouth, so we couldn’t take one outside to have a grand old time and potentially bring something back that could harm her sister,” says Padilla-Vaccaro.

Christian and Alysia Padilla-Vaccaro and their healthy twins Annabella (left) and Evangelina. Now with a newly-restored immune system, Evangelina lives a normal and healthy life. Courtesy of UCLA

The only treatments for SCID are bone marrow transplants from healthy people, ideally a matched sibling; the unaffected cells can then repopulate the immune system of the baby with SCID. But despite being her twin, Annabella wasn’t a blood match for her sister, nor were her parents. Padilla-Vaccaro and her husband, Christian, were considering unrelated donors but were concerned about the risk of rejection. “We would be trying to fix one problem and getting another,” she says.

MORE: Stem Cells Allow Nearly Blind Patients to See

That’s when the doctors at the Children’s Hospital at Orange County, where Evangelina was diagnosed, told her parents about a stem cell trial for SCID babies at UCLA, led by Dr. Donald Kohn. “As soon as they said trial, I thought, ‘my kid is dead,” says Padilla-Vaccaro of the last resort option. But a dozen children born with other forms of SCID—in which different mutations caused the same weak immune systems—who were successfully treated by Kohn convinced the couple that the therapy was worth trying. Kohn had one spot left in the trial and was willing to hold it for Evangelina until she matured more. Born premature, she was diagnosed at six weeks old and needed more time for what was left of her immune system to catch up to weather the procedure.

When she was two months old, Evangelina was admitted to UCLA and had bone marrow drawn from her tiny hip. It contained the stem cells that go on to develop into all of the cells in the blood and immune systems. Kohn treated them with gene therapy, co-opting a modified virus to carry the healthy ADA gene so it could infect the stem cells from Evangelina’s bone marrow. The idea was that by transplanting these healthy ADA-containing cells back into Evangelina, she would soon be making her own healthy immune cells. And because they were made from her own cells, her body wouldn’t reject them.

MORE: Woman Receives First Stem Cell Therapy Using Her Own Skin Cells

“After the transplant of this miraculous tube of stem cells, which literally took five minutes, we had to just wait and see for a good six weeks,” says Padilla-Vaccaro. “The week after Christmas [in 2012], Dr. Kohn came in and told me, ‘It worked.’ It worked. Those words…besides the birth of my children, that day will always be the best day in my life.”

The success was a long time coming for Kohn as well. His group has been researching the best way to treat SCID with gene therapy for more than two decades. In the first trial, in 1993, they used cord blood, treating it with the healthy ADA gene and hoping enough of them would “take” to rebuild an immune system. It didn’t work.

In 2001, they tried a different way of delivering the precious gene in four patients. That failed as well.

MORE: Type 1 Diabetes Treatment Gets Boost from Stem Cells

Then, in 2009, he and his team began the trial that Evangelina eventually joined. After reading about a group in Italy that completely obliterated the patients’ existing immune systems with chemotherapy first, before introducing the new bone marrow cells to repopulate the system, Kohn tried that strategy on 10 babies. “Of all the patients we treated, all have had good immune reconstitution,” he says. “Within a month or two, we start seeing cells appear in the blood that are making the missing gene. When they are six months old or so, their immune systems are good enough for them to go out and not be protected, and by age two, they are pretty stable—their immune systems are reset.”

That’s where Evangelina is now, able to finally enjoy the world outside her home and the hospital. She got her first kisses from her parents when she was 18 months old. “My worry was that I couldn’t raise my daughter without her sister,” says Padilla-Vaccaro. “Now I don’t have to.”

TIME Brain

New Hope for Replacing Nerves Damaged by Parkinson’s Disease

Stem cells may provide a new way of regrowing the motor neurons affected by the movement disorder

Reporting in the journal Cell Stem Cell, scientists say that stem cells turned into motor nerves function nearly identically to fetal motor nerves: the kind now used to treat some patients with Parkinson’s disease. That could mean that the stem cells may become an important source of new nerves to replace the ones damaged in diseases like Parkinson’s.

In Parkinson’s, motor nerves that normally produce dopamine, which is critical for regulating muscle movements and controlling dexterity, are damaged, and dopamine levels drop dramatically. The researchers, led by Malin Parmar, an associate professor of regenerative neurobiology at Lund University, took human embryonic stem cells extracted from excess IVF embryos and treated them to develop into motor neurons. They transplanted these neurons into the brains of rats bred to develop Parkinson’s and found that the lab-made cells brought dopamine levels in these animals back to normal levels in five months. The nerves sent out long extensions to connect with other nerve cells in the brain—such networks are important to ensuring coordinated and regulated muscle movements, and without them, patients experience uncontrollable tremors. The effects were similar to those seen when fetal nerves are transplanted into Parkinson’s patients, a treatment currently used to help alleviate symptoms in some patients.

While the results are exciting, it’s just the first step in bringing stem cell-based treatments to human patients. The study did not delve into how well the new neurons functioned and whether they could reverse symptoms of Parkinson’s in the animals. And even if they do improve those symptoms, scientists still have to show that humans could get the same effects. In an editorial accompany the article, Roger Barker of Addenbrooke’s Hospital and the University of Cambridge warned that the exciting possibilities of stem-cell based therapies shouldn’t push scientists—or patients—to expect too much too soon. Before the cells can be tested in people, he writes, it’s necessary to have “a knowledge of what the final product should look like and the need to get there in a collaborative way without being tempted to take shortcuts, because a premature clinical trial could impact negatively on the whole field of regenerative medicine.”

TIME medicine

Stem Cells Allow Nearly Blind Patients to See

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Stem cells could lead to new treatments for eye disorders Photography by Peter A. Kemmer—Getty Images/Flickr RF

Embryonic stem cells can be turned into a therapy to help the sight of the nearly blind

In a report published in the journal Lancet, scientists led by Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology, provide the first evidence that stem cells from human embryos can be a safe and effective source of therapies for two types of eye diseases—age-related macular degeneration, the most common cause of vision loss in people over age 60, and Stargardt’s macular dystrophy, a rarer, inherited condition that can leave patients legally blind and only able to sense hand motions.

In the study, 18 patients with either disorder received transplants of retinal epithelial cells (RPE) made from stem cells that came from human embryos. The embryos were from IVF procedures and donated for research. Lanza and his team devised a process of treating the stem cells so they could turn into the RPE cells. In patients with macular degeneration, these are the cells responsible for their vision loss; normally they help to keep the nerve cells that sense light in the retina healthy and functioning properly, but in those with macular degeneration or Stargardt’s, they start to deteriorate. Without RPE cells, the nerves then start to die, leading to gradual vision loss.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions Like Alzheimer’s

The transplants of RPE cells were injected directly into the space in front of the retina of each patient’s most damaged eye. The new RPE cells can’t force the formation of new nerve cells, but they can help the ones that are still there to keep functioning and doing their job to process light and help the patient to see. “Only one RPE can maintain the health of a thousand photoreceptors,” says Lanza.

The trial is the only one approved by the Food and Drug Administration involving human embryonic stem cells as a treatment. (Another, the first to gain the agency’s approval, involved using human embryonic stem cells to treat spinal cord injury, but was stopped by the company.) Because the stem cells come from unrelated donors, and because they can grow into any of the body’s many cells types, experts have been concerned about their risks, including the possibility of tumors and immune rejection.

MORE: Early Success in a Human Embryonic Stem Cell Trial to Treat Blindness

But Lanza says the retinal space in the eye is the ideal place to test such cells, since the body’s immune cells don’t enter this space. Even so, just to be safe, the patients were all given drugs to suppress their immune system for one week before the transplant and for 12 weeks following the surgery.

While the trial was only supposed to evaluate the safety of the therapy, it also provided valuable information about the technology’s potential effectiveness. The patients have been followed for more than three years, and half of the 18 were able to read three more lines on the eye chart. That translated to critical improvements in their daily lives as well—some were able to read their watch and use computers again.

“Our goal was to prevent further progression of the disease, not reverse it and see visual improvement,” says Lanza. “But seeing the improvement in vision was frosting on the cake.”

TIME diabetes

Type 1 Diabetes Treatment Gets Boost from Stem Cells

Human stem cell derived beta cells
Insulin-making cells grown from stem cells glow green two weeks after they are transplanted into mice (c) Douglas Melton 2014

Scientists started with stem cells and created the first insulin-making cells that respond to changes in glucose

Scientists are closer to a potential stem cell treatment for type 1 diabetes.

In a new article in the journal Cell, Douglas Melton, co-director of the Harvard Stem Cell Institute (and one of the 2009 TIME 100) and his colleagues describe how they made the first set of pancreatic cells that can sense and respond to changing levels of sugar in the blood and churn out the proper amounts of insulin.

It’s a critical first step toward a more permanent therapy for type 1 diabetics, who currently have to rely on insulin pumps that infuse insulin when needed or repeated injections of the hormone in order to keep their blood sugar levels under control. Because these patients have pancreatic beta cells that don’t make enough insulin, they need outside sources of the hormone to break down the sugars they eat.

MORE: Stem-Cell Research: The Quest Resumes

Melton started with two types of stem cells: those that come from excess embryos from IVF procedures, and those that can be made from skin or other cells of adults. The latter cells, known as iPS cells, have to be manipulated to erase their developmental history and returned back to an embryonic state. They then can turn into any cell in the body, including the pancreatic beta cells that produce insulin. While the embryonic stem cells from IVF don’t require this step, they aren’t genetically matched to patients, so any beta cells made from them may cause immune reactions when they are transplanted into diabetic patients.

Both techniques, however, produced similar amounts of insulin-making beta cells—something that would have surprised Melton a few years ago. But advances in stem cell technology have made even the iPS cells pretty amenable to reprogramming into beta cells. Melton’s group tested more than 150 different combinations of more than 70 different compounds, including growth factors, hormones and other signaling proteins that direct cells to develop into specific cell types, and narrowed the field down to 11 factors that efficiently turned the stem cells into functioning beta cells.

MORE: Woman Receives First Stem Cell Therapy Using Her Own Skin Cells

The two populations of stem cells churned out hundreds of millions of insulin-making cells, which is the volume of cells that a patient with type 1 diabetes would need to cure them and free them from their dependence on insulin. An average patient, says Melton, would need one or two “large coffee cups” worth of cells’, each containing about 300 million cells. Melton and his team then conducted a series of tests in a lab dish to confirm that the cells were functioning just like normal beta cells by producing more insulin when they were doused with glucose, and less when glucose levels dropped. That was a huge advance over previous efforts to make beta cells from stem cells—those cells could produce insulin, but they didn’t respond to changing levels of glucose and continuously pumped out insulin at will.

Next, the scientists transplanted about five million of the stem cell derived beta cells into healthy mice, and two weeks later, gave them an injection of glucose. About 73% of the mice produced enough insulin to successfully break down the sugar. What’s more, that was similar to the proportion of mice responding to glucose after getting a transplant of beta cells from human cadavers. That was especially encouraging since some type 1 diabetics currently receive such transplants to keep their diabetes under control. “We’ve now shown that we can produce an inexhaustible source of beta cells without having to do to cadavers,” he says.

MORE: First Stem Cells Cloned From Diabetes Patient, Thanks to Egg Donors

Taking the tests even further, the group showed that even mice that were already diabetic showed improved blood sugar levels after receiving a transplant of the stem cell beta cells—in other words, the transplanted cells effectively cured their diabetes. “We showed you can give three sequential challenges of glucose—similar to breakfast, lunch and dinner—and the cells responded properly,” says Melton.

But he acknowledges that as exciting as the advance is, it only solves half the problem for those with type 1 diabetes. The reason their beta cells aren’t able to make enough insulin may be due to the fact that they are attacked by the body’s own immune system for reasons that scientists still don’t understand. So the next step in turning these findings into a potential therapy is to find ways to protect the beta cells from destruction, either by encapsulating them in a mesh-like device similar to a molecular tea bag, or finding ways to genetically modify them to carry ‘don’t attack me’ proteins, the same way that fetal cells do so that an expectant mother’s immune cells don’t attack the growing baby.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimer’s

“It’s taken me 10 to 15 years to get to this point, and I consider this a major step forward,” says Melton, who began researching ways to treat type 1 diabetes when first his son, then his daughter were diagnosed with the condition more than two decades ago. “But the longer term plan includes finding ways to protect these cells, and we haven’t solved that problem yet.”

TIME medicine

Woman Receives First Stem Cell Therapy Using Her Own Skin Cells

A Japanese woman is the first to receive retinal cells made from her own skin cells

Researchers at the RIKEN Center for Developmental Biology in Japan surgically transplanted a sheet of retinal pigment cells into the eye of a 70-year old woman on Friday.

The cells are the first induced pluripotent stem cells, or iPS cells, given to a human patient. They were made by Masayo Takahashi, who grew them from the patient’s own skin cells, which were treated with four genetic factors to revert back to an embryonic-like state. Takahashi then soaked the cells with the appropriate growth factors and other compounds so they developed into retinal pigment cells.

The patient was losing her sight due to macular degeneration, because her retinal pigment endothelial cells were damaged by an overgrowth of blood vessels. Replacing them with a new population of cells can restore her sight.

MORE: Stem-Cell Research: The Quest Resumes

Stem cell scientists are starting to test their treatments in eye-related diseases, because parts of the eye are protected from the body’s immune system, which could recognize the introduced cells as foreign and destroy them. That’s not a problem with the iPS cells, since they are made from the patient’s own skin cells, but it’s an added safety net to ensure that the therapy is safe and hopefully effective.

Because iPS cells are genetically treated to erase their skin cell development and revert them back to an embryonic-like state when they can become any type of cell, there are still concerns about their safety when transplanted into patients. The U.S. Food and Drug Administration has not yet approved a trial involving iPS cells – so far, only stem cells made from excess IVF embryos have been approved for treating macular degeneration. A 19-member committee of the Japanese ministry of health approved the experimental procedure four days ago, according to Nature, after Takahashi made her case, with the help of Dr. Shinya Yamanaka of Kyoto University, who shared the 2012 Nobel Prize for discovering iPS cells.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimer’s

Japan’s stem cell scientists are hoping the surgery is a success; the field has been struggling since a well-publicized paper about a new way to make iPS cells was retracted amid allegations of fraud.

It’s not known whether the cells will continue to grow and form abnormal tumors, or whether they will migrate to other parts of the body. But now that the first patient has received them, those questions – and more, about the effectiveness of stem cell therapy – might be answered soon.

TIME Japan

Science Scandal Triggers Suicide, Soul-Searching in Japan

Sasai, deputy director of the Riken's Center for Developmental Biology, poses for a photo with Haruko Obokata in front of a screen showing STAP cells, in Kobe
Yoshiki Sasai, right, deputy director of the Riken's Center for Developmental Biology, poses for a photo with Haruko Obokata on Jan. 28, 2014. Kyodo/Reuters

Yoshiki Sasai’s death has generated mixed emotions among Japan's scientific community

It was a success story that Japan sorely needed: a young, talented and beautiful researcher developed a cheap and simple way to grow versatile stem cells.

The discovery promised to usher in a new age of regenerative medicine, validated Japan as a leader in scientific research and demonstrated that even in a male-dominated society, women could excel when given a chance.

Alas, it may have been too good to be true.

Intrigued by researcher Haruko Obokata’s breakthrough, other scientists tried but failed to replicate her results. Peer-review websites accused her of falsifying data and doctoring images, and supervisors were accused of lax management. Obokata, 30, was forced to retract her scientific papers, and the government-sponsored research center where she worked launched a formal investigation.

The matter took a darker turn this week when Obokata’s supervisor and mentor, Yoshiki Sasai, a noted scientist in his own right, was found hanging from a stairway railing at his office.

In farewell letters found at his desk, Sasai reportedly apologized for the turmoil, but urged Obokata to continue her work and to prove her detractors wrong.

Sasai’s death cast a pall over the controversy. But in a nation where suicide does not carry the same stigma as in some Western countries, there has been a certain degree of sympathy — if not outright approval.

“This is seen in some respects as an honorable way out of a shameful and devastating turn of events: ‘A highflyer brought low by an underling’s mistakes, seeking to atone for and expunge the shame,’” says Jeffrey Kingston, a professor of Asian studies at Tokyo’s Temple University-Japan. “This touches a chord of sympathy and understanding in Japan.”

Sasai was a noted stem-cell scientist and deputy director of the RIKEN Center for Developmental Biology, in Kobe — part of a national research system that receives roughly $1 billion a year in government support and is part of an ambitious effort to boost scientific research throughout Japan.

The 52-year-old was not directly involved in Obokata’s research, but had helped recruit her and supervised the research papers that were published in the British journal Nature in January.

But whether Sasai’s death generates sympathy for Obokata or the rest of Japan’s scientific community remains to be seen.

Obokata burst onto the scene in late January with the publication of the Nature papers, of which she was the lead author. Those studies claimed to have found a new way of creating stem cells, dubbed stimulus-triggered acquisition of pluripotency, or STAP. Such cells could be used to create new tissue, with potential for treating illnesses like Alzheimer’s, heart disease and stroke.

Poised and photogenic, Obokata was an instant hit with Japan’s frenetic media —mainstream and social, alike. Here, after all, was a different kind of scientist. Even in the lab, Obokata flashed stylish clothes, false eyelashes and fashionable hairstyles. She eschewed the usual white lab coat in favor of a traditional housewife’s kappogi (a gift from her grandmother, she explained) and had the walls of her lab painted pink and yellow and decorated with cartoon characters.

Even Prime Minister Shinzo Abe, who has made “womenomics” a key plinth of his economic revival package, noticed. He commended Obokata’s apparent achievement from the floor of Japan’s Parliament and vowed to build “a country where the women are the brightest in the world.”

But it didn’t take long for doubts to surface. Peer-review websites noticed oddities and discrepancies in Obokata’s research. Attempts to replicate her findings failed.

By mid-February, RIKEN had launched an internal investigation. In April, officials charged Obokata with fabricating data, doctoring images and borrowing descriptions from other research papers.

Meanwhile, discrepancies were found in the research of other leading scientists, though none with the public profile of Obokata.

In an excruciating, four-hour press conference televised live by many of Japan’s major networks, a tearful Obokata struggled to maintain her composure. She admitted errors in her research papers, but maintained they were innocent mistakes that did not affect the final results. STAP cells were real, she insisted.

She has remained on the staff at RIKEN but has maintained a low profile, refusing interviews. In July, RIKEN officials announced that she would be allowed to take part in a five-month experiment designed to discover once and for all whether her initial findings were real. Other researchers and video cameras would monitor her work, officials said.

The RIKEN affair has been watched closely by Japan’s scientific community, which has produced its share of Nobel Prizes but is often viewed as insular and underperforming.

“One thing that should not be lost in all this is that Japan produces outstanding science,” says Jonathan Dorfan, a former director of the Stanford Linear Accelerator Center, at Stanford University, and now president of the Okinawa Institute of Science and Technology in Japan.

“People in the scientific community here are paying attention to this, and hopefully that will lead to the kind of training that will avoid an outcome like this happening again.”

TIME Stem Cells

Blockbuster Stem-Cell Studies Retracted Because of Fraud

Editors of Nature, which published two papers claiming to generate stem cells in a simplified way, are retracting both papers after data was “misrepresented.”

In an editorial published on Wednesday, editors at the scientific journal Nature announced their decision to retract two papers that received wide media attention, including by TIME, for apparently dramatically simplifying the process of creating stem cells. Genetically manipulating older, mature cells are the only confirmed methods for reprogramming them back to their embryonic state, but in the Nature papers, Japanese scientists claimed to have accomplished the feat by physical means, using an acidic bath or physical stress.

Several months after the papers were published, one of the co-authors, from the RIKEN Institute, called for their retraction, saying “I’m no longer sure that the articles are correct.” RIKEN’s own probe determined that the studies’ lead author, Haruko Obokata, was guilty of misconduct.

At the time, Nature launched its own investigation into concerns that some of the figures in the paper contained errors, and that parts of the text were plagiarized. The journal now says that “data that were an essential part of the authors’ claims have been misrepresented. Figures that were described as representing different cells and different embryos were in fact describing the same cells and the same embryos.”

MORE: Stem-Cell Scientist Guilty of Falsifying Data

While scientific journals have peer-review processes to check researchers’ work, they rely on the fact that the scientists are presenting their data in their entirety and without any biases—something that didn’t occur in this case.

Nature’s editors say they are reviewing their review process and intend to improve on the way they select articles to ensure that such mistakes are minimized.

TIME

First Stem Cells Cloned From Diabetes Patient, Thanks to Egg Donors

The feat could lead to new cell-based treatments for the disease, but it relies on the willingness of women to donate their eggs

Is donating eggs to scientists for a research study any different from donating eggs to a couple hoping to have a baby using in vitro fertilization (IVF)? That’s a question that stem cell researchers — and policy makers — have been wrestling with ever since it became possible to “clone” cells with a technique involving eggs and skin cells. The debate is bound to heat up again thanks to a breaking study published today in the journal Nature: for the first time, scientists have generated stem cells from a patient with a disease. And last week, researchers did the same with skin cells from two healthy men.

Nuclear transfer—the cloning process that created Dolly the sheep, the first mammal to be cloned—has more important implications for humans than creating mini-mes. The technique, which involves taking adult cells and inserting them into an egg stripped of its own DNA (so the donor genes can be erased and reprogrammed to develop into any type of cell in the human body) holds promise as a way to treat and even cure a host of diseases ranging from diabetes to Alzheimer’s. But for years, the barrier to perfecting the process using human cells has been the dearth of eggs available for study.

While women have been donating eggs for decades to help infertile couples conceive through in vitro fertilization (IVF) — and getting paid around $8,000 for their trouble — ethicists have flagged concerns about compensating women who want to donate eggs for research purposes, despite the fact that the procedure is medically identical. The lack of compensation has deterred women from enrolling in stem cell studies, for example, since the process requires two weeks of daily doctor visits, injections and tests, as well as a surgical procedure to remove the eggs. “When we surveyed women who donated to IVF cycles and were compensated, and said would you be wiling to do it without compensation, do you know what? They’re not. And why would they be?” says Dr. Mark Sauer, chief of reproductive endocrinology at Columbia University who has recruited egg donors for IVF cycles for decades.

In a research context, some ethicists have said, such payment, while not for the eggs themselves but for women’s time and effort, could be coercive, and therefore exploit women who may be economically less able to resist the offers. The concern has led some states, such as Massachusetts and California, to prohibit compensating women who donate eggs to research studies. And scientists can’t use federal dollars to pay women to donate eggs for research.

But in New York, policy makers who believed that donating eggs to research studies was equivalent on ethical grounds to donating for IVF purposes, passed a law in 2009 that allowed women to be compensated up to $10,000, as they would for donating to IVF cycles. That allowed Dieter Egli, a stem cell scientist at the New York Stem Cell Foundation, and his colleagues to finally achieve success in using the technique to create stem cells from a patient – in this case, a 32 year old woman with type I diabetes. He was able to use funds from a grant from New York State Stem Cell Science as well as private sources including the New York Stem Cell Foundation and the Russell Berrie Foundation Program in Cellular Therapies of Diabetes.

MORE: Scientists Report First Success in Cloning Human Stem Cells

Egli’s report — the one published in the journal Nature — could mean that diabetic patients may one day be able to make their own insulin-producing cells to replace their no longer functioning ones. Other patients needing to replace diseased or damaged cells may also benefit; those with Alzheimer’s could, for example, generate new neurons to replace ones involved in memory and cognition that have been lost to the neurodegenerative condition.

The feat was only possible, however, because 35 women agreed to donate 512 eggs for the study — and get compensated for their contribution. “It’s a lot of effort. To do it for no money, no compensation, would be really asking a lot, especially given the risks,” says Hannah, one of the women who agreed to donate her eggs for the study but requested a pseudonym to protect her privacy. Those risks include changes in hormone levels that can cause hot flashes, sleep disruptions, mood swings, as well as more severe but rare complications such as blood clots and kidney failure. Hannah, 32, has donated eggs to two IVF cycles as well as to this research. “The process is basically identical. So in terms of being compensated for the time and effort it took, from that perspective only, it deserves equal compensation,” she says.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimer’s

Sauer, a co-author on the paper, was responsible for approaching women like Hannah who were recruited to donate for IVF cycles and ask them about whether they would be willing to donate their eggs to the stem cell study for the same compensation. Most agreed. He stresses that the compensation is not for “buying” the eggs but for the time and inconvenience of participating in the study. “To me, it always seemed insulting, to ask if they would be willing to [donate] for free to research when they could get $8,000 donating for IVF,” he says.

Could the fee be considered high enough that it’s coercive? Possibly, but if it’s not considered unethical in an IVF scenario, and the process is identical, why would it be any more suspect in a research setting? “The possibility that [my eggs] may become a living being is not more valid to me than if they become something that can help a person who is already alive,” says Hannah. And the procedure is time consuming and risky. All told, agreeing to become a donor involves weeks of disruptions, starting with the two weeks of daily appointments at the hospital for hormone injections or ultrasounds and culminating in the surgical procedure under general anesthesia to extract the eggs, which can take an entire day including the recovery. That’s followed by a few weeks of refraining from intercourse until the next menstrual period. “It’s about a month of changing your lifestyle,” says Hannah.

But thanks to donors like her, not only have Egli and his group created stem cells from the diabetic patient, they have also coaxed them to develop into insulin-producing cells that respond to glucose when transplanted into a mouse model for diabetes. He argues that the technology could potentially lead to life-saving treatments for patients, since the cells made from the process are the patient’s own, and won’t be rejected by their immune systems if transplanted. “In my opinion, we should learn to use a patient’s own cells,” Egli told reporters in a teleconference discussing the results. “I think that is going to become a reality.”

That is, as long as laws continue to allow women willing to donate eggs for research studies to be compensated just as women who donate eggs to IVF cycles. “It’s part of my body that is not being used,” says Hannah of her decision to participate in the research. “When I do hear things in the news about diseases like childhood diabetes, my ears perk up, and I wonder if at some point I’ll be hearing about the use of stem cells in developing some kind of prevention or treatment, and if my eggs contributed to that.”

TIME

Researchers Clone Cells From Two Adult Men

After years of failed attempts, researchers have successfully generated stem cells from adults. The process could provide a new way for scientists to generate healthy replacements for diseased or damaged cells in patients

After years of failed attempts, researchers have finally generated stem cells from adults using the same cloning technique that produced Dolly the sheep in 1996.

A previous claim that Korean investigators had succeeded in the feat turned out to be fraudulent. Then last year, a group at Oregon Health & Science University generated stem cells using the Dolly technique, but with cells from fetuses and infants.

MORE: Stem-Cell Research: The Quest Resumes

In this case, cells from a 35-year-old man and a 75-year-old man were used to generate two separate lines of stem cells. The process, known as nuclear transfer, involves taking the DNA from a donor and inserting it into an egg that has been stripped of its DNA. The resulting hybrid is stimulated to fuse and start dividing; after a few days the “embryo” creates a lining of stem cells that are destined to develop into all of the cells and tissues in the human body. Researchers extract these cells and grow them in the lab, where they are treated with the appropriate growth factors and other agents to develop into specific types of cells, like neurons, muscle, or insulin-producing cells.

Reporting in the journal Cell Stem Cell, Dr. Robert Lanza, chief scientific officer at biotechnology company Advanced Cell Technology, and his colleagues found that tweaking the Oregon team’s process was the key to success with reprogramming the older cells. Like the earlier team, Lanza’s group used caffeine to prevent the fused egg from dividing prematurely. Rather than leaving the egg with its newly introduced DNA for 30 minutes before activating the dividing stage, they let the eggs rest for about two hours. This gave the DNA enough time to acclimate to its new environment and interact with the egg’s development factors, which erased each of the donor cell’s existing history and reprogrammed it to act like a brand new cell in an embryo.

VIDEO: Breakthrough in Cloning Human Stem Cells: Explainer

The team, which included an international group of stem cell scientists, used 77 eggs from four different donors. They tested their new method by waiting for 30 minutes before activating 38 of the resulting embryos, and waiting two hours before triggering 39 of them. None of the 38 developed into the next stage, while two of the embryos getting extended time did. “There is a massive molecular change occurring. You are taking a fully differentiated cell, and you need to have the egg do its magic,” says Lanza. “You need to extend the reprogramming time before you can force the cell to divide.”

While a 5% efficiency may not seem laudable, Lanza says that it’s not so bad given that the stem cells appear to have had their genetic history completely erased and returned to that of a blank slate. “This procedure works well, and works with adult cells,” says Lanza.

The results also teach stem cell scientists some important lessons. First, that the nuclear transfer method that the Oregon team used is valid, and that with some changes it can be replicated using older adult cells. “It looks like the protocols we described are real, they are universal, they work in different hands, in different labs and with different cells,” says Shoukhrat Mitalopov, director of the center for embryonic cell and gene therapy at Oregon Health & Science University, and lead investigator of that study.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimer’s

Second, the findings confirm that the key factor in making nuclear transfer work with human cells is not the age of the donor cell, as some experts have argued, but the quality of the donor egg. “No matter how much you tweak the protocols or optimize them, it looks like the major player in efficiency is the individual egg quality,” says Mitalipov. He notes that all of his stem cell lines came from the same egg donor. The two cell lines described by Lanza’s group also came from one egg donor.

This latest success should reignite the debate over which reprogramming method generates the most reliable, and potentially useful, stem cells for eventually treating patients. The nuclear transfer method may join two other ways of making stem cells: one, developed by James Thomson in 1998, relied on extracting them from days-old embryos left over from IVF, and another, developed by Japanese scientist Shinya Yamanaka in 2006 (and for which he was awarded the Nobel Prize), bypassed the egg and embryo completely, allowing researchers to make stem cells by modifying an adult’s cells using a mixture of just four genes.

MORE: Stem Cell Researcher Calls for Retraction of His Own Work

Each method has it advantages and risks, however. IVF embryos are difficult to come by, since they require permission from couples to be used for stem cells research, and they may not be genetically matched to patients who might benefit from cells they generate.

While so-called induced pluripotent stem cells, or iPS cells, avoid the need for embryos and could be matched to patients, some studies suggest that the process may not completely reprogram cells, leaving populations of some partially reprogrammed ones in the mix. In addition, iPS cells aren’t useful for treating mitochondrial diseases, which result from mutations in the cell’s energy factories, which have their own DNA outside of the cell’s DNA in the nucleus. If a cell with a mitochondrial mutation is reprogrammed using the iPS technique, any mutations would be reprogrammed as well.

MORE: FDA Approves Second Trial of Stem-Cell Therapy

Nuclear transfer, however, could treat these disorders since it involves an egg that provides its own, healthy mitochondria. But the process requires a good supply of eggs, which have to be donated by healthy volunteers. That raises ethical concerns since the technique could produce human clones. That’s why research on nuclear transfer is not funded by the federal government, and scientists know less about these cells and their potential than they do about iPS cells. “They have become kind of like cursed cells,” says Mitalipov of the stem cells generated through nuclear transfer. “But we clearly need to understand more about them.”

For patients who might one day benefit from stem cell-based therapies, that understanding could mean the difference between life and death, which is why the latest findings are potentially significant. “We have another way to skin the cat,” Lanza says. “The hope is that iPS cells work out, but for the future application of stem cell therapies to treating disease, it’s good knowing there is another way to make stem cells should we need to.”

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