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Mice with muscle injuries obtained increased muscle mass with stem cell transplant

Researchers from the University of Colorado at Boulder have found that loss of muscle function and mass, which is a result of aging, can be prevented by transplanting certain types of stem cells into the legs of mice. 

Bradley Olwin, study leader and professor of CU-Boulder's molecular, cellular and developmental biology department, along with co-authors John K. Hall, Glen Banks and Jeffrey Chamberlain, have discovered that mice with limb muscle injuries can be repaired by injecting muscle stem cells from donor mice into the leg muscle. 

Olwin and his team made the discovery by drawing between 10 and 50 stem cells as well as attached myofibers, which are individual skeletal muscles, from healthy three-month old mice, and transplanted the stem cells into three-month-old injured mice. These muscle stem cells were found in populations of satellite cells, which repair and maintain skeletal muscles and are located between muscle fibers and nearby connective tissue. 

Only days after the injection, the injury was repaired. In addition, the treated muscle increased 50 percent in mass with a 170 percent increase in size, and was able to sustain itself throughout the rest of the mouse's life, which was about two years.

"We found that the transplanted stem cells are permanently altered and reducing the aging of the transplanted muscle, maintaining strength and mass," said Olwin. 

Researchers expected the transplanted cells to be injected into the injured muscle, repopulate, repair the muscle and dissipate. But they were shocked when the cells constantly maintained the repaired muscle. 

"In this study, the hallmarks we see with the aging of muscles just weren't occurring," said Olwin. "The transplanted material seemed to kick the stem cells to a high gear for self-renewal, essentially taking over the production of muscle cells. But the team found that when transplanted stem cells and associated myofibers were injected to healthy mouse limbs muscles, there was no discernible evidence for muscle mass growth.

"The environment that the stem cells are injected into is very important, because when it tells the cells there is an injury, they respond in a unique way. We don't yet know why the cells we transplanted are not responding to the environment around them in the way that the cells that are already there respond. It's fascinating, and something we need to understand."

Researchers flagged donor cells in injured mice by using green fluorescent protein, which glows under ultraviolet light. They found that several transplanted cells were fused to myofibers and that the number of satellite cells had increased. 

"It's our hope that we can someday identify small molecules or combinations of small molecules that could be applied to endogenous muscle stem cells of humans to mimic the behavior of transplanted cells," said Olwin. "This would remove the need for cell transplants altogether, reducing the risk and complexity of treatments."

This study was published in Science Translational Medicine on November 10.

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