Scientists at the Harvard Stem Cell Institute and the Columbia University Medical Center in the US have reprogrammed the skin cells of two patients with amyloid lateral sclerosis (ALS), making induced pluripotent stem cells (iPS cells). The stem cells were then used to generate motor neurons - the nerve cells that degenerate in patients with ALS.
The researchers will use the motor neurons generated from the patients' skin to study how the disease develops, and as a new approach to drug testing. 'Our study now shows that we can generate hundreds of millions of motor neurons that are genetically identical to a patient's own neurons. This will be an immense help as we try to uncover the mechanisms behind the disease and screen for drugs that can prolong life,' said Professor Christopher Henderson, who led the research with Professor Kevin Eggan.
The research represents the first time that iPS cells have been generated from an individual with a known genetic condition. This new technique for creating embryonic-like stem cells circumvents the need to use human eggs or embryos to generate stem cells. First described by Professor Shinya Yamanaka at Kyoto University in 2007, iPS cells are generated by introducing four key stem cell genes into adult human skin cells. The reprogrammed skin cells are pluripotent - they have the potential to grow into any other cell type in the body, such as nerve cells.
In the study, published in the journal Science, the researchers used the skin of two elderly sisters with a known genetic mutation in the gene superoxide dismutase 1, which causes ALS. By inserting the four genes into the skin cells' DNA, iPS cells were generated from the skin biopsy. They then treated the iPS cells with chemicals that induce the cells to transform into motor neurons. Motor neurons are nerve cells that convey information from the brain and spinal cord to muscles in the body, and these cells degenerate and die as the ALS disease progresses, ultimately leading to limb paralysis and death in patients.
Studying the degeneration of motor neurons from ALS patients was previously not possible because it is not possible to isolate them from a patient's spinal cord. 'No one has ever managed to isolate these neurons from a patient and grow them in a dish', Professor Eggan said. Professor Henderson agreed: 'up until now, it's been impossible to get access to the neurons affected by ALS', but also cautioned that 'we don't yet know how similar [the motor neurons derived from the patients' iPS cells] are to the motor neurons in ALS patients'.
The same approach could be used to study other genetic disorders, such as Parkinson's and Huntington's disease. Professor Ian Wilmut, Director of the Centre for Regenerative Medicine at the University of Edinburgh, and famous for creating Dolly the cloned sheep, said: 'Overall, it is likely that this will be one of the most important uses of stem cells during the next 10 to 20 years'.
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