'Blank' stem cells showing promise
Could quiet debate on embryos
Cambridge scientists have used stem cells that were "reprogrammed" from ordinary skin cells to alleviate symptoms of Parkinson's disease in rodents, illustrating the vast medical potential of this new type of stem cell.
In the study, rats whose midbrains were damaged in a way to closely mimic Parkinson's received transplants of healthy neurons cultivated from reprogrammed stem cells. These are basically biological "blank slates" that are believed to have the same capacity as embryonic stem cells to be turned into nerves, organs, bloods, bone, or any other cell type.
The brain-damaged rats had wandered in uncontrollable circles. After the treatment, however, eight of the nine test rats "showed markedly less or even no circling," according to Marius Wernig, a scientist at the Whitehead Institute for Biomedical Research and lead author of the research.
"This is the first demonstration that reprogrammed cells can integrate into the neural system or positively affect neurodegenerative disease," Wernig said.
The work, published yesterday in the journal Proceedings of the National Academy of Sciences, has political as well as medical significance since it may add weight to the argument - made by President Bush, among other religious conservatives - that there is no compelling reason to use human embryos to make stem cells. Reprogrammed cells are created from ordinary tissue without harming embryos. The work at the Whitehead, a Cambridge-based center loosely affiliated with the Massachusetts Institute of Technology, was done with rats, but the principle applies to humans.
"This shows that [reprogrammed] cells are able to function in the therapeutic manner that people have ascribed to them," said Rudolf Jaenisch, the pioneering Whitehead and MIT stem cell scientist who oversaw the work. "These cells are more readily available and much less controversial than embryonic stem cells. But they seem to have identical potential."
Jaenisch's lab has already achieved success in using reprogrammed cells to treat sickle cell anemia, a blood disease, in lab rodents.
"The basic idea is to use [reprogrammed] stem cells to make custom-designed healthy cells that will not be rejected by a patient," said Jaenisch. Since the new cells can be reprogrammed from the patient's own tissue, they are genetically identical.
But researchers concede that the direct therapeutic use in humans remains problematic because the reprogrammed cells are forged in a process that relies on potent regulator genes that are linked to cancer - raising the potential that they might trigger tumors in patients.
"In a human, we'd use the same process - taking adult cells, reprogramming it to the [stem cell] stage, then differentiating it into the cells we need," said Jaenisch. "But human work is a long way off. Science moves step by step."
Last year saw a series of breakthroughs in the creation of embryonic-like stem cells without making or destroying human embryos, winning applause from religious conservatives who had opposed the use of stem cells derived from cloned or frozen embryonic tissue.
The research from the Whitehead offers dramatic evidence that so-called IPS cells - for induced pluripotent stem cells - hold medical potential equal to the fanfare that greeted their appearance as an alternative to embryonic stem cells.
"This is a big step forward," said Margaret Sutherland, a program director at the National Institute of Neurological Disorders and Strokes. "IPS cells are still in their infancy. But this shows their use [in human medicine] could be near for things like drug screening" or in diagnosing patients.
The day is fast nearing when skin cells, for example, could be taken from a patient and quickly transformed into stem cells that can be used to test the efficiency of a specific medicine against a given disease - an individual's own flesh and blood, in the form of tissue made from reprogrammed cells, could be used to see if it is responsive to particular medicine or other therapy.
Parkinson's disease is a degenrative disorder caused by insufficient levels of a key brain signaling chemical, called dopamine. As many as 1 million Americans suffer from the disease, which results in loss of motor control.
The research at Whitehead was similar to work done earlier in the decade by Harvard Medical School and McLean Hospital in Belmont that used "pure" embryonic stem cells to relieve symptoms of Parkinson's disease in rats. The efficacy of true embryonic stem cells has been recognized for years, but reprogrammed cells are still uncharted territory.
The Whitehead researchers started with adult mouse skin cells, which were treated with four genes to regress into an embryonic stem cell-like state. In lab dishes, these cells were then coaxed into becoming brain tissue. This is the neural matter that was implanted into the brains of Parkinson's-afflicted rats - raw material from mice works fine in rats, at least in this experiment.
Within eight weeks of the transplant, the neurons generating dopamine were established in the rats' brains, alleviating symptoms of the disease.
"This is a proof-of-principle for using reprogrammed . . . cells for treating disease," said George Q. Daley, a prominent stem cell researcher at Children's Hospital Boston.
The revolutionary reprogramming technique, introduced using human cells only last year by scientists in Japan and the United States, uses genetic alteration to turn back the clock on adult cells, making them regress to an embryonic-like state. Then the time machine process can be reversed, with the cells coaxed to take on the form and function of any developed cell.
Colin Nickerson can be reached at nickerson@globe.com. 