Scientists say they have proved the viability of a new way to study diseases using a patient's own cells. Yesterday, a team from Harvard and Columbia universities announced that they have generated a population of motor neurons--nerve cells that control muscle movement--from the skin cells of an 82-year-old woman with amyotrophic lateral sclerosis (ALS). Such cells provide a way to take ALS studies "out of the patient and into the petri dish," Harvard biologist Kevin Eggan said at a press conference.
For many illnesses, researchers would like to study the diseased cells from a patient in the lab; their ultimate hope is that they can also fix those cells by modifying them genetically and then inject them back into the patient. Until recently, scientists believed the way to do this would be through therapeutic cloning, a controversial technique--still unproven for humans--that involves putting the nucleus from a body cell into an enucleated egg. The resulting cells can then be coaxed to differentiate into any bodily tissue type.
The ethical problems of using eggs can be circumvented with induced pluripotent stem (iPS) cells, which are adult cells reprogrammed to behave like embryonic stem cells. In 2006, scientists created such cells from mice and rats by introducing a combination of four genes to a culture of skin cells. Then last year, scientists showed that they could do the same thing with human cells. The new study, published online today by Science, shows that iPS cells can be successfully generated even from the skin cells of an elderly, sick person, Eggan says.
ALS involves the progressive degeneration of spinal cord motor neurons, leading to paralysis of limbs and respiration. The team, led by Eggan and Christopher Henderson of Columbia University Medical Center, grew iPS cells by introducing the four genes used in the earlier studies into about 30,000 skin cells from the patient. Among the hundreds of colonies that grew from these cells, the scientists found that a handful had markers for pluripotency. To these iPS cell lines the scientists added molecules known to guide mammalian pluripotent cells into nerve cells. A significant proportion of them showed markers characteristic of motor neurons. Further tests--such as injecting the cells into mouse or chick embryos to see if they establish proper connections--will be needed to see if they are full-fledged neurons.
The woman had a familial form of ALS caused by a mutation in the gene called superoxide dismutase 1, or SOD1, which is responsible for only 2% of ALS cases. Ninety-five percent of ALS cases are "sporadic"--meaning there is no known inherited mutation; many probably result from genetic changes occurring through life interacting with environmental influences. Nonetheless, said Eggan, "I think this approach has incredible promise for studying other forms of ALS." The symptoms of the familial and the sporadic forms of ALS are so similar, he added, that they probably share many common mechanisms.
"It is exciting that they have generated human cells from the patient material," says stem cell researcher Jeffrey Rothstein of Johns Hopkins University in Baltimore, Maryland, who also studies ALS. But he warns that for the cells to be useful in research, they have to be exactly the same as those causing disease in the patient. "You don't want a partial replicate of the motor neuron," Rothstein says. iPS-generated neurons, he says, may be of little use in replicating the fate of motor cells buffeted by a lifetime of drug exposure and other metabolic and environmental influences.