This is a major landmark for stem cell therapy. Motor neurons derived from embryonic stem cells were implanted into paralyzed rats, which partially restored their ability to move like normal. A team of researchers at John Hopkins used a unique method to encourage the new spinal nerves to connect to muscles: a combination of transplanted motor neurons, chemicals that stimulate axon growth, and nerve growth factors. (More under the fold.)
"This work is a remarkable advance that can help us understand how stem cells might be used to treat injuries and disease and begin to fulfill their great promise. The successful demonstration of functional restoration is proof of the principle and an important step forward. We must remember, however, that we still have a great distance to go," says Elias A. Zerhouni, Director of the National Institutes of Health.
"This study provides a 'recipe' for using stem cells to reconnect the nervous system," says Dr. Kerr. "It raises the notion that we can eventually achieve this in humans, although we have a long way to go."
The team first cultured mouse embryonic stem cells, and manipulated them to differentiate into motor neurons. Just before transplantation, the researchers added nerve growth factors as well as dibutyl cAMP (dbcAMP) to the neurons. dbcAMP has been shown to reduce the inhibition of axonal growth which myelin causes. The cell mixture was transplanted into 8 groups of rats, each group received a slightly different "recipe" of growth factors and supporting factors. Some groups received Rolipram prior to injection (also helps to counteract axonal inhibition). Some groups received GDNF-secreting cells as well as motor neurons. GDNF is a chemical which attracts neurons towards it.
Three months post-transplant, the team compared the groups of rats to see which one fared the best. Their results indicated that the rats which received motor neurons, Rolipram, dbcAMP, and the GDNF-secreting cells has several hundred transplant-derived axons connecting into the peripheral nervous system, more than any other group. This group even had axons which extended to the lower leg, forming functional synapses with the muscles there! They had improved 50% (from completely paralyzed vs normal) in 4 months after the transplant, and 75% after 6 months. After 6 months, the rats could bear weight on their legs and use them to push off surfaces. None of the other rat groups ever recovered any function at all.
This is extremely exciting research, as it shows that stem cells cannot only slow down or help repair an injury, but can actually replace lost neurons and form new, correct connections. There are a multitude of human disorders that could be treated, if not cured, but such a method.
Source: This study is published in the July 2006 issue of Annals of Neurology. (Deshpande D, Kim YS, Martinez T, Carmen J, Dike S, Shats I, Rubin L, Drummond J, Krishnan C, Hoke A, Maragakis N, Shefner J, Rothstein J, Kerr D. "Recovery from Paralysis in Adult Rats Using Embryonic Stem Cells." Annals of Neurology, July 2006, Vol. 60, No. 1, pp. 22-34.)