Muscle derived stem cells

Muscle Derived Stem Cell-- Research at the Stem Cell Research Center

By: Burhan Gharaibeh
Using a modification of the pre-plate technique, Dr. Johnny Huard and his laboratory ([www.pitt.edu/~huardlab]) have isolated 3 populations of myogenic cells from normal mouse skeletal muscle on the basis of adhesion characteristics and proliferation behavior of the digested muscle cells. The resultant cells are two major cell fractions, an early or rapidly adhering fraction (RAC) and a late or slowly adhering fraction (SAC). The RAC fraction is similar in morphology and markers to fibroblasts and satellite cells. SAC cells retain their phenotype for more than 30 passages and can differentiate into various lineages, including muscle, neural, osteogenic, and endothelial. More importantly, the transplantation of the SAC cells, in contrast to satellite cell transplantation, significantly improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. Dr. Huard therefore believe that the SAC cells represent a novel population of muscle-derived stem cells (MDSCs) that will significantly improve muscle cell mediated therapies. His research main goal is to determine whether transplanted MDSCs can deliver dystrophin and lead to improvements in both the structure and function of dystrophic muscle and further investigate the ability of these MDSCs to ameliorate the function of dystrophic muscle. Huard is also performing experiments to determine whether the isolation method or the age and condition of the skeletal muscle source influence the cells’ biological properties. In addition, research at the Stem Cell Research Center (SCRC) are working to evaluate the relative importance of MDSC survival, self-renewal, and pluripotent behavior on the improved transplantation capacity of these cells. Finally, the investiagators are studying the use of systemic delivery of MDSCs to achieve dystrophin delivery and improve function in dystrophic muscle that is inaccessible via intramuscular injection. Dr. Burhan Gharaibeh has some limited data showing that MDSC can be delivered to newborn mice via the temporal vein. However, the majority of those cells end up in the capillary bed in the lung and the protocol has to be optimized. This project continues to increase our understanding of myogenic cell populations that display stem cell characteristics and may open new alternatives to improve muscle regeneration in dystrophic muscle via transplantation of MDSCs.

Tracking Stem Cells

A major issue in stem cell transplantation is tracking the injected cells to validate if they are differentiating into the desired cell type or if they are fusing to the local tissue without any improvement in function. Check this web site for other links to Dr. Burhan Gharaibeh on tracking the injected MDSCs in several animal tissues. [www.pit.edu/~burhan]

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