Stem cells reverse rat paralysis

A team from Johns Hopkins University School of Medicine has managed to partially restore movement in paralysed rats using mouse embryonic stem cells (ES cells) and a cocktail of chemical enhancers. Research leader Douglas Kerr described the work as 'a blueprint for how to rewire part of the nervous system'. It is the first time that stem cells have been successfully used to reconnect a destroyed part of the nervous system, previous studies have overcome blockages or scar tissue in damaged systems but this new study uses stem-cell-derived neurons to completely replace destroyed nerves. The procedure re-established the electrical path from the rat brains through the spinal cord and out to the limb muscles.

The researchers took 120 paralysed adult rats and injected them with mouse ES cells that had been chemically primed in the lab to differentiate into motor neurons. The rats were then divided into eight groups in order to receive different combinations of additives that the researchers predicted may improve the recovery mediated by stem cells. The groups variously received stem-cell-derived-neurons that had been treated to increase survival and promote axon (nerve fibre) growth, some received drugs to reduce the inhibitory effect of myelin (the protective nerve sheath) on axon outgrowth and some received a factor to attract transplanted axons toward the skeletal muscle target. The team then examined the level of nerve re-growth in the affected muscle, took electrophysiological recordings to determine the level of electrical signalling being transmitted in the affected areas and examined the rats for signs of recovery from paralysis.

The researchers found that after six months only the rats in the group that had received all of the extra chemical enhancers had function restored, although this was only partial and did not happen in all of the rats. Eleven of the 15 rats in this key test group were able to put weight on and step off from the paralysed hind paw that the stem cells had targeted. The rats in this key group made 125 new nerve connections to skeletal muscle of which 50 reached the affected hind paw and were functional. Rats from the other groups showed similar numbers of surviving neurons from the transplant but without the additional chemical enhancers this did not mediate recovery from paralysis.

'This is an important first step, but it really is a first step, a proof of principle that you can rewire part of the nervous system', said Dr Kerr. The group plans to follow up this research with experiments on pigs to see if the greater distances between the spinal cord and limbs proves to be an obstacle. Discussing the possibility of one day using these techniques to help humans suffering from multiple sclerosis, paralysis and other neurological disorders, Dr Kerr commented, 'It's not imminent, but it is a realistic hope. It used to be science fiction, but it is now a realistic possibility'. The work is published in the Annals of Neurology and was funded by organisations including the National Institutes of Health and the Muscular Dystrophy Association.