Research Brief: Deriving muscle stem cells from teratomas

July 20, 2018

Researchers in the University of Minnesota Medical School have developed a process to regenerate skeletal muscle cells in animal models with muscular dystrophy. The unlikely source of those cells is a type of benign tumor called a teratoma that produces cells of all types, including glands and hair follicles.

Michael Kyba, Ph.D., professor and Lillehei Endowed Scholar in the Medical School, and his colleagues in the Lillehei Heart Institute and the Stem Cell Institute describe their work in seeking a source of cells to rebuild muscle in a new study published in Cell Stem Cell.

The researchers investigated cells from animal teratomas and found that by refining and sorting cells they were able to purify a population of cells that could rebuild skeletal muscle in mice with muscular dystrophy. Outcomes showed improved potential to regenerate muscle to an extent beyond results researchers have seen before.

The researchers injected a small number of teratoma derived cells into a diseased muscle and found that they regenerated 80 percent of this muscle versus the 5 to 10 percent regeneration currently possible. Importantly, the teratoma-derived cells also populated the newly formed muscle with muscle stem cells, endowing the new muscle with the ability to regenerate itself should future injury occur.

Other important measures of muscle effectiveness including tetanic force, specific force and fatigue time showed the teratoma cell-generated muscled showed significant improvement over the control muscle.

“The goal of this research was to seek in unexplored places a source of cells that, when transplanted, would rebuild skeletal muscle and demonstrate significant improvements in muscle strength and resilience,” said Kyba, the lead author of the study.

“We did not study spontaneously arising pathological teratomas,” said Sunny Chan, Ph.D., co-author and an assistant professor in the Medical School. “Instead, we created teratomas using undifferentiated pluripotent cells injected into an immunodeficient mouse, and found that among their many cell types, the resulting teratomas contained muscle stem cells.”

While the results are promising, the researchers note that the main advance is the ability to generate cells of tremendous regenerative potential for study as opposed to therapy at this point.  

Although the newly-formed muscles showed no signs of the teratomas from which they were derived or any other adverse events, safety is paramount and fail-safe measures would need to be implemented before considering therapeutic applications. Therefore, further study will be required to move this research forward beyond animal model studies.

Funding for this study was provided by the National Institutes of Health, Regenerative Medicine Minnesota and the Greg Marzolf Jr. Foundation.

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