Stem Cells from Muscle Can Repair Nerve Damage After Injury
Stem cells derived from human muscle tissue were able to repair nerve damage and restore function in an animal model of sciatic nerve injury, according to McGowan Institute for Regenerative Medicine faculty members Johnny Huard, PhD, Professor in the Departments of Orthopaedic Surgery, Microbiology and Molecular Genetics, Bioengineering, Pathology, Pediatrics, and Physical Medicine and Rehabilitation and the Director of the Stem Cell Research Center, and Donna Stolz, PhD, Associate Director of the Center for Biologic Imaging, University of Pittsburgh School of Medicine, and Associate Professor in the Departments of Cell Biology and Pathology at the University of Pittsburgh, and researchers at the University of Pittsburgh School of Medicine. The findings, published in the Journal of Clinical Investigation, suggest that cell therapy of certain nerve diseases, such as multiple sclerosis, might one day be feasible.
To date, 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 Dr. Huard.
“This study indicates that placing adult, human muscle-derived stem cells at the site of peripheral nerve injury can help heal the lesion,” Dr. Huard said. “The stem cells were able to make non-neuronal support cells to promote regeneration of the damaged nerve fiber.”
The researchers, led by Dr. Huard and Mitra Lavasani, PhD, 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.
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,” Dr. Lavasani said. “This approach has great potential for not only acute nerve injury, but also conditions of chronic damage, such as diabetic neuropathy and multiple sclerosis.”
Drs. Huard and Lavasani and the team are now trying to understand how the human muscle-derived stem/progenitor cells triggered injury repair, as well as developing delivery systems, such as gels, that could hold the cells in place at larger injury sites.
Dr. Huard is also the Henry J. Mankin, MD, Endowed Chair in Orthopaedic Surgery Research and also the Vice Chair for Musculoskeletal Cellular Therapeutics, Department of Orthopaedics, Pitt’s School of Medicine. In addition, he is the Deputy Director for Cellular Therapeutic Research at the McGowan Institute for Regenerative Medicine. Dr. Stolz is also the Director of the Cell Biology and Molecular Physiology Graduate Program.
Abstract (Human muscle-derived stem/progenitor cells promote functional murine peripheral nerve regeneration. Lavasani M, Thompson SD, Pollett JB, Usas A, Lu A, Stolz DB, Clark KA, Sun B, Péault B, Huard J. Journal of Clinical Investigation; online 2014 Mar 18.)