Long-Term Survival of Transplanted Stem Cells in Immunocompetent Mice with Muscular Dystrophy

Gregory Q. Wallace^*, Karen A. Lapidos^*, Jordan S. Kenik^* and Elizabeth M. McNally^*

From the Department of Medicine,^* Section of Cardiology, and the Departments of Molecular Genetics and Cell Biology and Human Genetics, The University of Chicago, Chicago, Illinois

Satellite cells refer to resident stem cells in muscle thatare activated in response to damage or disease for the regenerationand repair of muscle fibers. The use of stem cell transplantationto treat muscular diseases has been limited by impaired donorcell survival attributed to rejection and an unavailable stemcell niche. We isolated a population of adult muscle mononuclearcells (AMMCs) from normal, strain-matched muscle and transplantedthese cells into ${delta}$ -sarcoglycan-null dystrophic mice. Distinctfrom other transplant studies, the recipient mice were immunocompetentwith an intact endogenous satellite cell pool. We found thatAMMCs were 35 times more efficient at restoring sarcoglycancompared with cultured myoblasts. Unlike cultured myoblasts,AMMC-derived muscle fibers expressed sarcoglycan protein throughouttheir entire length, consistent with enhanced migratory ability.We examined the capacity of single injections of AMMCs to providelong-term benefit for muscular dystrophy and found persistentregeneration after 6 months, consistent with augmentation ofthe endogenous stem cell pool. Interestingly, AMMCs were moreeffectively engrafted into aged dystrophic mice for the regenerationof large clusters of sarcoglycan-positive muscle fibers, whichwere protected from damage, suggesting that the stem cell nichein older muscle remains permissive.