Reprogrammed pluripotent stem cells can be used to treat the symptoms of Parkinson's disease in mice, according to a new study published by researchers in the Proceedings of the National Academy of Sciences.1 Stem cells represent a promising source of healthy replacement cells for a panoply of degenerative diseases, but this is the first study to specifically use reprogrammed cells, known as induced pluripotent stem (iPS) cells, to combat Parkinson's. It builds on a major study they published last year in which iPS cells were used to treat sickle cell anemia in mice, demonstrating that iPS cells had real therapeutic potential.2

In the current study, the iPS cells, which share the characteristics of embryonic stem (ES) cells, were created in vitro from fibroblasts taken from the skin of adult mice. Next the researchers differentiated the ES-like cells into neuronal precursor cells and transplanted them into the brains of developing mice. The mice were born naturally and their brain tissue analyzed one to nine weeks after surgery. The results showed that the precursor cells differentiated into neurons and glia, integrated into the surrounding brain tissue and functioned normally.

Next, the researchers tested whether the iPS cells could be used therapeutically in a rat model of Parkinson's. So they transplanted more iPS-derived neuronal precursor cells into the midbrain region in rats that had been injured to mimic symptoms of the disease. (Injecting a toxin called 6-OH-DA kills off dopamine-producing cells, the sort that die of naturally in Parkinson's disease.) Four weeks later, the behaviour of Parkinsonian rats that had received replacement cells was markedly improved in comparison to sham-operated rats.

In a similar set of experiments, researchers at Memorial Sloan-Kettering Cancer Center recently used somatic cell nuclear transfer (SCNT) to generate ES cells, which they then used to treat Parkinson's in mice.3 However, iPS cells have several advantages: Unlike SCNT, iPS does not involve the use of embryos, so it is much less controversial. It is also easier to perform.

“This work is a really big step forward, but it raises other questions, the biggest of which is how safe these cells would be,” says Xianmin Zeng, who studies cell replacement therapies for Parkinson's disease at the Buck Institute for Age Research in California. Safety is an issue with iPS because the reprogramming mechanism is not well understood and because reprogramming involves the use of retroviruses, which may disrupt the genome or cause cancer.

Taken together, the two studies raise the possibility that pluripotent stem cells may one day replace fetal cells, which are currently being studied to treat Parkinson's disease. “The fact that fetal cells can't be standardized is a big problem for transplantation,” says Zeng. “ES cells cultured under the same conditions are identical, and they can be characterized in vitro. So patients would receive the same amount and the same standard of cells.”

In the meantime, more research is needed to determine whether transplanted ES cells will survive and function over time in host tissue. Large numbers of dopamine-producing fetal cells, transplanted into patients with Parkinson's disease in the 1990s, have survived for up to 16 years, but two of three recent reports in Nature Medicine4,5,6 suggest that the disease spreads to some of the transplanted cells.