A research group from the University of California, San Francisco have isolated and characterized human muscle stem cells. In addition, they have established that these stem cells can robustly replicate and repair damaged muscles when they are grafted onto an injured site. These remarkable findings might open the door to potential treatments for patients with severe muscle injuries, paralysis or genetic diseases that adversely affect skeletal muscles (e.g., muscular dystrophy).
Jason Pomerantz, MD is an assistant professor of plastic and reconstructive surgery at UCSF, and served as the managing author of this work. “We’ve shown definitively that these are bona-fide stem cells that can self-renew, proliferate and respond to injury,” said Pomerantz.
Badly damaged muscles can suffer terrible depletion of their native populations of stem cells or even obliteration of the stem cell niches and populations. Since such muscles have lost the very things that can heal them, these muscles will not be able to heal the damage they have sustained. This very fact represents a terrible hurdle for physicians who specialize in patients who have been crippled by muscle injury and paralysis. One of the worse cases is those conditions that cause damage or paralysis in the critical small muscles of the face, hand and eye, according to Pomerantz.
When muscles are badly damaged, they can lose the native populations of stem cells that are needed to heal. This has posed a major roadblock for treating patients crippled by muscle injury and paralysis, particularly in the critical small muscles of the face, hand and eye, Pomerantz said.
Fortunately, there have been remarkable surgical advances in restoring nerves in damaged muscles. Unfortunately, if the healing process takes too long, the stem cell pool is exhausted and the regenerative capacity is attenuated and eventually. Such injured muscles fail to connect to the nerve tissue and without accompanying motor and sensory nerves, skeletal muscles then to degenerate.
“This is partly why we haven’t had major progress in treating these patients in 30 years,” Pomerantz said. “We know we can get the axons there, but we need the stem cells for there to be recovery.”
A group of stem cells called “satellite cells” line the borders of muscle fibers and, in mice, can function as stem cells and contribute to muscle growth and repair. Until now, however, it wasn’t clear whether human satellite cells worked the same way. It was also terribly unclear how to isolate muscle satellite cells from human tissue samples or even adapt them to help treat patients with muscle damage.
Pomerantz and colleagues tackled this problem used muscle tissue from surgical biopsies of muscles of the head, trunk and leg. Then they used antibody staining to show that human satellite cells can be identified by the expression of the transcription factor PAX7 in combination with the cell-surface proteins CD56 and CD29. Pomerantz and his colleagues use this molecular signature to isolate populations of human satellite cells from these patient biopsies. Then they grafted these satellite cells into mice with damaged muscles whose own muscle stem-cell populations had been depleted. Five weeks after the transplantation, these human cells had successfully integrated into the mouse muscles and divided to produce families of daughter stem cells; effectively replenishing the stem cell niche and repairing the damaged muscle tissue.
This characterization of human muscle stem cells and the ability to transplant them into injured muscles has varied and wide-ranging implications for patients who are presently suffering from muscle paralysis, whose damaged muscles have lost the ability to regenerate. Additionally, protocols that allow us to isolate and manipulate human stem cells also may have applications for understanding why our muscles lose their regenerative capacity during normal aging or in the case of genetic diseases such as muscular dystrophy.
“This gives us hope that we will be able to extract healthy stem cells from other muscles in the patient’s body and transplant them at the site of injury,” Pomerantz said. “If replenishing a healthy muscle stem cell pool facilitates reinnervation and recovery, it would be a significant leap forward.”
These findings appeared the Sept. 8 edition in the open access Cell Press journal, Stem Cell Reports.