Researchers use new adult stem cell technique in possible Parkinson’s treatment

Cambridge, England, Apr 9, 2008 / 05:13 am

A new study from scientists at Harvard and the Massachusetts Institute of Technology reports that reprogrammed skin cells can become functioning neurons when transplanted into the brains of mice and rats.

In what the MIT Technology Review calls a “proof of concept” finding, the researchers report that the cells can improve symptoms in a rat model of Parkinson’s disease.

The use of the reprogrammed cells, called induced pluripotent stem cells (iPS), could sidestep ethical and logistical obstacles that afflict stem cell research which destroys human embryos.

The research team, led by Rudolph Jaenisch at the Whitehead Institute for Biomedical Research at MIT, published its results in the “Proceedings of the National Academy of Sciences.”  The researchers used a previous method for reprogramming cells in which the skin cells of a mouse can be made pluripotent when infected with a retrovirus carrying four specific genes.

The scientists established that these modified mouse skin cells could be turned into functioning neurons in a culture.  They then transplanted the neurons into the brains of fetal mice.  When the mice reached adulthood, the researchers examined the mice’s brains and identified the transplanted cells, which they had labeled with a fluorescent marker.

According to Marius Wernig, a postdoctoral fellow at the Whitehead Institute, the cells “migrate nicely” into the brain and mature there.  "They adopt functions of mature neurons," he explained.

The researchers also tested whether the cells could repair damaged dopamine neurons in rats. This would reveal if the cells could help alleviate Parkinson’s disease, since it involves the loss of these dopamine producing neurons.

According to the study, rats that had damaged dopamine neurons were given transplants of neurons derived from the iPS cells. The scientists noted an improvement in the motor skills problems associated with Parkinson’s.

John Gearhart, a stem cell biologist at John Hopkins School of Medicine who was not involved in the study, said that previous studies of the iPS cells had conflicting results.  Some studies showed the cells performing similarly to embryonic stem cells, while other studies did not.  According to the MIT Technology Review, Gearhart said the latest study was important because it compared the iPS-derived cells with neurons derived from embryonic stem cells.

At present, the iPS cells are considered unsafe for human use because the way they are created has the potential to cause cancer.  Two of the four genes used in the retrovirus are known as oncogenes, also known as tumor promoters, which help cells proliferate. 

Tumors have also been observed in experiments with embryonic stem cells.

According to Wernig, the next major effort is "to try to reprogram human cells without the use of a retrovirus and without oncogenes," perhaps by targeting the genes with drugs.

Induced pluripotent stem cells avoid using and destroying embryos created through so-called therapeutic cloning, a process that itself involves technical challenges and ethical problems.  If iPS cells come from a patient’s own skin, there would be no potential complications from the immune system’s rejection of foreign tissue.