14 April 2008
ByAppeared in BioNews 453
Nerve tissue derived from stem cells made from reprogrammed skin developed into normal brain tissue and relieved symptoms of Parkinson's disease in rats, in a study published in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) last week. Scientists at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts and the Massachusetts Institute of Technology, US, showed for the first time that nerves developed from so-called induced pluripotent stem cells (iPS cells) can form functional brain tissue.
Last year, the group were among the first to develop iPS cells by treating mouse skin cells with a combination of genetic factors. Two independent groups then successfully generated human iPS cells. These cells resemble embryonic stem cells (ES cells) and can develop into different body tissues, but do not require the creation and destruction of an embryo.
'These cells are more readily available and much less controversial than embryonic stem cells. But they seem to have identical potential', said team leader Rudolf Jaenisch last year.
In the latest study, Jaenisch, Marius Wernig and colleagues first developed nerve precursor cells from iPS cells and transplanted them into the brains of developing mice. After nine weeks, the iPS-derived cells had migrated and grown into several distinct subtypes of nerve tissue in the brains of the newborn mice.
'They were all over the place and they were electrically integrated. They looked like they were really functional cells', explained Jaenisch.
Motion difficulties in Parkinson's disease arise from a lack of the brain signalling chemical dopamine, due to the death of dopamine-producing neurons. The researchers made iPS cells develop into dopamine neurons, and used them to treat rats given symptoms of Parkinson's disease. The rats' dopamine neurons were chemically damaged in the striatum, an area of the brain involved in motion control, leading to difficulties in balancing and walking. Of the nine rats in the study, eight showed marked improvement in motion and dopamine activity four weeks after the differentiated cells were transplanted.
'This is the first demonstration that reprogrammed cells can integrate into the neural system or positively affect neurodegenerative disease', Wernig said.
'These iPS cells could be used for generating functional dopaminergic neurons that could have therapeutic value', added Jaenisch.
Since iPS cells can be created by reprogramming cells from patients, the potential for individually targeted stem cell therapy for Parkinson's disease is highlighted by this research. However, experimental grafting cannot yet be performed in humans. The genetic factors used to generate iPS cells could lead to tumour formation, and the safety of the viral vectors used in their production is also unknown. Finally, the rat model of Parkinson's disease does not precisely mimic the complex processes of the condition in humans. Further development of the techniques used to create iPS cells will be necessary, it seems, before their medical applications can be realised.