Researchers from the University of Pittsburgh School of Medicine have discovered that stem cells derived from human muscle tissue can repair nerve damage and restore function in an animal model of sciatic nerve injury. These data have been recently published online in the Journal of Clinical Investigation, but more importantly, this work demonstrates the feasibility of cell therapy for certain nerve diseases, such as multiple sclerosis.
Presently there are few treatments for peripheral nerve damage. Peripheral nerve damage can leave patients with chronic pain, impaired muscle control and decreased sensation.
The senior author of this work, Henry J. Mankin, serves as the Chair in Orthopedic Surgery Research, Pitt School of Medicine, and deputy director for cellular therapy, McGowan Institute for Regenerative Medicine, and said, “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.”
Workers in Mankin’s laboratory, in collaboration with Dr. Mitra Lavasani, assistant professor of orthopedic surgery, Pitt School of Medicine, grew human muscle-derived stem/progenitor cells in culture by using a culture medium suitable for nerve cells. In culture, Lavasani, Mankin and their colleagues found that when these muscle-derived stem cells were grown in the presence of specific nerve-growth factors, they differentiated into neurons and glial cells. Glial cells act as support cells from neurons. One type of glial cell that these muscle-derived stem cells could differentiate into was Schwann cells, which are the cells that form the myelin sheath around the axons of neurons to accelerate the speed at which nerve impulses are conducted.
Mankin and his colleagues then injected these human muscle-derived stem/progenitor cells into mice that had a quarter-inch injury in their right sciatic nerve. The sciatic nerve controls right leg movement. Six weeks later, the nerve had fully regenerated in stem-cell treated mice, but the untreated group showed only limited nerve regrowth and functionality. In other tests, 12 weeks after treatments, the stem cell-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 that their gait, which had been abnormal, was now completely normal. Finally, treated and untreated mice experienced loss of muscle mass after nerve damage, but only the stem cell-treated mice regained normal muscle mass by 72 weeks after nerve damage.
“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. They are also developing delivery systems, such as gels, that could hold the cells in place at larger injury sites.
The co-authors of this paper included Seth D. Thompson, Jonathan B. Pollett, Arvydas Usas, Aiping Lu, Donna B. Stolz, Katherine A. Clark, Bin Sun, and Bruno Péault, all of whom are from the University of Pittsburgh.