Published in the journals Nature and Cell Stem Cell, new findings represent true milestones not only in the field of stem cell research, but in the broader discipline of early biological development.

iPSC (Induced Pluripotent Stem Cells) results duplicated
at Kyoto, Harvard, MIT
Led by Shinya Yamanaka at Kyoto University, one group successfully coaxed a mouse skin cell to reverse its development and return to an embryonic stage at which it produced stem cells. Two other groups based at Harvard Stem Cell Institute (HSCI) and the Whitehead Institute for Biomedical Research at MIT obtained similar results working independently. In the final paper, Kevin Eggan, also at HSCI, showed that even fertilized mouse zygotes at the one-cell stage can be reprogrammed to generate stem cells. Previously, biologists had believed that once fertilized embryos embarked on the developmental path, they could not be manipulated to produce stem cells.

So how does this science affect the millions of patients banking on the promise of stem cell therapies? Each of the investigators stresses that their results, while exciting, have not yet been tested with human cells, although those studies are already under way. But the basic principles involved in generating stem cells in mice and man are the same, and with a few modifications the scientists hope to have similar success with human cells. “It’s likely to be the case that since this discovery is based on such fundamental cell biology principles that the overarching rules [for mouse and human cells] are the same,” says Eggan. “There are subtleties in human embryology that make human development different, but it should work.”

Implications of iPSCs for human patients
If it is indeed possible to take a skin cell from an adult patient and tweak it to revert to an embryonic type cell, that would mean that any patient needing a stem cell-based treatment could, in theory, heal himself. Last year Yamanaka was the first to announce success with this approach by exposing the cells to four growth factors and nutrients. But the stem cells he generated were genetically abnormal and unstable. Building on the initial technique, Yamanaka’s group, as well as those led by Rudolph Jaenisch at Whitehead and Konrad Hochedlinger at HSCI, showed that the process does indeed work and can generate stable stem cells that go on to develop into eggs and sperm that can produce healthy mice.

Obstacles
One immediate obstacle to translating the results to human cells involves the way that the scientists turned back time on the mouse skin cells. They used vector, piggybacking the genes for the growth factors and proteins onto this infectious ferry. Retroviruses, however, like HIV, can cause infectious diseases and are not always easy to control, so before testing this approach in humans, researchers need to find other modes of transport for the critical compounds. The good news is that they need the genes to churn out their proteins for only a brief period of time, so using less virulent viruses, such as adenovirus (responsible for the common cold) or simply saturating the cell with growth factors and nutrients directly may work.

Two of the four factors that can turn back the clock on adult cells so efficiently are known to cause cancer. One, in fact, was the first gene discovered to cause cancer in mice. “Figuring out how to reprogram cells without directly exposing the cell to the cancer-causing effect of these genes is a major area of scientific activity and would have to occur before we could consider using similar factor in humans,” says Eggan.

Source: Time Magazine’s Health & Science Department, March 1, 2009.

Meanwhile the continuing success of adult stem cells marches on.

Adult Stem Cell resarch reverses effects of
Parkinson's Disease in human trial

Los Angeles, CA

Adult neural stem cell transplantation safe and effective
UCLA researchers have published the long-term results of a trial in the February issue of the Bentham Open Stem Cell Journal describing the results of the world’s first clinical trail using autologous neural stem cells for the treatment of Parkinson’s disease.

“We have documented the first successful adult neural stem cell transplantation to reverse the effects of Parkinson’s disease and demonstrated the long-term safety and therapeutic effects of this approach,” says lead author Dr. Michel Levesque.

The paper describes how Levesque’s team was able to isolate patient-derived neural stem cells, multiply them in-vitro, and ultimately differentiate them to produce mature neurons before they are reintroduced into the brain.

Immunosuppressants unnecessary
The team was able to inject the adult stem cells without the need for immunosuppressants. Unlike embryonic stem cells, adult stem cell injections don’t cause a patient’s immune system to reject the cells. The adult stem cells were highly beneficial for the patient involved in the study.

Amazing results
“Of particular note are the striking results this study yielded. For the five years following the procedure, the patient’s motor scales improved by over 80% for at least 36 months,” Levesque wrote.

He said he hoped a larger clinical trial would replicate the findings.

Dr. David Prentice, a former biology professor at Indiana State University who is now a fellow with the Family Research Council, says the results of the study are wonderful news for patients. “This evidence had been presented previously, but we now have the peer-reviewed scientific evidence for the effectiveness of adult stem cells in alleviating Parkinson’s symptoms,” he said. “While the data show that the technique needs refinement, this patient went for several years with little to no symptoms of his disease, even with only half of the brain treated with his own adult stem cells.”

Adult stem cells outpace embryonic stem cells
Prentice says the results continue to prove that adult stem cells outpace their embryonic counterparts. “People need to take notice that it is not embryonic stem cells that provide promise of treatments in the future, but rather it is adult stem cells that are already providing safe and effective therapies for patients now, without the problems of rejection or tumors,” Prentice explains.

“We need to pour our resources, especially taxpayer dollars, into adult stem cell research to foster more and better treatment and put the patients first,” he said.

Levesque is a principal investigator for NeuroGeneration, a biotechnology company, and is affiliated with the UCLA School of Medicine and the Brain Research Institute.

Adult stem cell research trials
could reduce need for heart transplants

London, England

Upcoming trial offers hope for heart disease treatment
Heart disease patients in England, who may otherwise need a transplant, could soon participate in a trial involving the use of adult stem cells that may reduce or eliminate the need for the transplant. The trials, if successful, could show another capability of the ethical version of stem cells.

Adult stem cells have been used for years to repair heart damage in patients, but scientists at London’s King’s College Hospital are hoping that this pioneering treatment can take them to the next level.

The treatment involves taking a patient’s own stem cells and growing them in a lab setting. The bone marrow cells are turned into human heart stem cells and then injected into the heart to repair damage.

Animal trials successful
The researchers have already tested the process on animals with considerable success and Dr. Jonathan Hill, a hospital consultant who hopes to work with scientists at King’s College London University, tells the London Telegraph that human trials could begin within a year.

Professor Sian Harding of Imperial College London told the Telegraph that the trials could result in a “big leap forward” in helping patients who suffer from heart failure.

ESC research "years away" from same success
The adult stem cells overcome one of the primary problems associated with embryonic stem cells – that they are rejected by a patient’s immune system. “Placi- Harding is working on trying to turn embryonic stem cells into heart cells using the same process, and she admitted to the newspaper that that work is “years away’ from achieving the same success as adult stem cells.

Other heart treatment research using adult stem cells
In March 2005 researchers at Johns Hopkins University started what was then believed to be the first clinical trial to use adult mesenchymal stem cells to repair muscle damaged by heart attack. The Hopkins team presented their research on animals at the November 2004 American Heart Association conference. The team found that 75% of dead scar tissue disappeared after therapy, and they hoped to replicate the success with humans.

Last year the University of Utah was enrolling patients in a new clinical trial that uses their own bone marrow adult stem cells to treat two types of heart failure.

The trial is the first of its kind for a condition called cardiomyopathy, which is not susceptible to other forms of treatment besides a heart transplant.

Meanwhile, German researchers have enjoyed success (not yet used in human trials) in building heart valves using the “scaffolding concept” and adult stem cells derived from umbilical cord blood.

The scientist in charge of the research noted that the valves might be used to replace defective ones in children, perhaps even growing along with them and allowing them to avoid the multiple surgeries required by traditional valve replacement.