Skeletal Muscle Regenerative Potential of Human MuStem Cells following Transplantation into Injured Mice Muscle

Abstract

After intra-arterial delivery in the dystrophic dog, allogeneic muscle-derived stem cells, termed MuStem cells, contribute to long-term stabilization of the clinical status and preservation of the muscle regenerative process. However, it remains unknown whether the human counterpart could be identified, considering recent demonstrations of divergent features between species for several somatic stem cells. Here, we report that MuStem cells reside in human skeletal muscle and display a long-term ability to proliferate, allowing generation of a clinically relevant amount of cells. Cultured human MuStem (hMuStem) cells do not express hematopoietic, endothelial, or myo-endothelial cell markers and reproducibly correspond to a population of early myogenic-committed progenitors with a perivascular/mesenchymal phenotypic signature, revealing a blood vessel wall origin. Importantly, they exhibit both myogenesis in vitro and skeletal muscle regeneration after intramuscular delivery into immunodeficient host mice. Together, our findings provide new insights supporting the notion that hMuStem cells could represent an interesting therapeutic candidate for dystrophic patients.

Cell therapy to improve regeneration of skeletal muscle injuries

“…Among these are muscle‐derived stem cells (MDSCs) and CD133+ mesoangioblasts that closely resemble pericytes . MDSCs are not terminally committed to the myogenic lineage and can differentiate into the mesodermal lineages as evidenced by their myogenic, osteogenic, and chondrogenic potential . Transplantation of MDSCs into severe muscle injury models has improved muscle repair and reduced fibrosis, with some of the observed effects being attributed to their secretome .…”

Biomaterial and stem cell‐based strategies for skeletal muscle regeneration

“…To support these findings, Lorant et al found that when injecting perivascular stem cells into cryoinjured muscles of scid mice the cells integrated into host tissue and contributed to the production of structural proteins associated with differentiated myofibers. 92 In contrast, when Meng et al delivered muscle-derived pericytes intra-arterially to mice, they found that they did not contribute to the regeneration of muscle. 93 These authors believed the discrepancy in results were due to the differences in experimental techniques, animal models, and outcome measurements.…”

“…Further, this study also showed that when delivered systemically the pericytes can cross the vessel wall to colonize the injured muscle. To support these findings, Lorant et al found that when injecting perivascular stem cells into cryoinjured muscles of scid mice the cells integrated into host tissue and contributed to the production of structural proteins associated with differentiated myofibers . In contrast, when Meng et al delivered muscle‐derived pericytes intra‐arterially to mice, they found that they did not contribute to the regeneration of muscle .…”

Biological Basis of Treatments of Acute Muscle Injuries: A Short Review

“…34 Other approaches include the use of muscle-derived stem cells (MDSCs). They have been used in animal models of severe muscle injury 35,36 and muscular dystrophy, but there are no clinical studies. MDSCs are multipotent and have osteogenic and chondrogenic as well as myogenic potential, and they may be useful in injuries affecting different tissues such as the myotendinous junction.…”