Thursday, 20 March 2014

Muscle stem cells treat nerve damage in an animal model of sciatic nerve injury

Johnny Huard, PhD stem cell researcher
Johnny Huard, PhD
According to a new study by researchers at the University of Pittsburgh School of Medicine, stem cells derived from human muscle tissue can be used to repair nerve damage and restore function. The study was carried out in an animal model of sciatic nerve injury.

The findings indicate that cell therapy for certain nerve diseases, including multiple sclerosis, might one day be possible.

As of now, treatments for damage to peripheral nerves, which are the nerves outside the brain and spinal cord, have not been very successful, often leaving patients with impaired muscle control and sensation, pain and decreased function, said senior author Johnny Huard, Ph.D., professor of orthopaedic surgery, and Henry J. Mankin Chair in Orthopaedic Surgery Research, Pitt School of Medicine, and deputy director for cellular therapy, McGowan Institute for Regenerative Medicine.

“This study indicates that placing adult, human muscle-derived stem cells at the site of peripheral nerve injury can help heal the lesion. The stem cells were able to make non-neuronal support cells to promote regeneration of the damaged nerve fiber.” Dr. Huard said. 

The researchers, led by Dr. Huard and Mitra Lavasani, Ph.D., first author and assistant professor of orthopaedic surgery, Pitt School of Medicine, cultured human muscle-derived stem/progenitor cells in a growth medium suitable for nerve cells. They found that, with prompting from specific nerve-growth factors, the stem cells could differentiate into neurons and glial support cells, including Schwann cells that form the myelin sheath around the axons of neurons to improve conduction of nerve impulses.

Mitra Lavasani, Ph.D., stem cell researcher
Mitra Lavasani

In mouse studies, the researchers injected human muscle-derived stem/progenitor cells into a quarter-inch defect they surgically created in the right sciatic nerve, which controls right leg movement. Six weeks later, the nerve had fully regenerated in stem-cell treated mice, while the untreated group had limited nerve regrowth and functionality. Twelve weeks later, treated mice were able to keep their treated and untreated legs balanced at the same level while being held vertically by their tails. When the treated mice ran through a special maze, analyses of their paw prints showed eventual restoration of gait. Treated and untreated mice experienced muscle atrophy, or loss, after nerve injury, but only the stem cell-treated animals had regained normal muscle mass by 72 weeks post-surgery.

“Even 12 weeks after the injury, the regenerated sciatic nerve looked and behaved like a normal nerve. This approach has great potential for not only acute nerve injury, but also conditions of chronic damage, such as diabetic neuropathy and multiple sclerosis.” Dr. Lavasani said.

Drs. Huard and Lavasani and their team are now trying to understand how the human muscle-derived stem/progenitor cells triggered injury repair, as well as developing delivery systems, like gels, that could hold the cells in place at larger injury sites.

The project was supported by National Institutes of Health grants AR049684 and NS081724-01, the U.S. Department of Defense, the Henry J. Mankin Endowed Chair for Orthopaedic Research at the University of Pittsburgh, the William F. and Jean W. Donaldson Chair at Children’s Hospital of Pittsburgh of UPMC, the Hirtzel Foundation, and the Pittsburgh Claude Pepper Older Americans Independence Cente.

- Lavasani M, Thompson SD, Pollett JB, Usas A, Lu A, Stolz DB, Clark KA, Sun B, PĂ©ault B, & Huard J (2014). Human muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration. The Journal of clinical investigation PMID: 24642464

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