Volumetric muscle loss injury is a common health problem with long-term disabilities. One common treatment is using muscle flaps from donor site, which has limited potentials due to donor site availability and morbidity. Although several stem cell therapies have been evaluated so far, most suffer from limited availability, immune incompatibility, or differentiation potential. Therefore, induced pluripotent stem cells (iPSCs) have a great promise for this purpose due to their unique differentiation, self-renewal, and immunocompatibility. Current study was designed to determine therapeutic potential of human iPSCs (hiPSCs) in a mouse model of volumetric muscle loss. Muscles were subjected to excision to generate 30%-40% muscle loss. Next, hiPSCs were differentiated toward skeletal myogenic progenitors and used with fibrin hydrogel to reconstruct the lost muscle. Histologic evaluation of the treated muscles indicated abundant engraftment of donor-derived mature fibers expressing human markers. Donor-derived fibers were also positive for the presence of neuromuscular junction (NMJ), indicating their proper innervation. Evaluation of the engrafted region indicated the presence of donor-derived satellite cells expressing human markers and Pax7. Finally, in situ muscle function analysis demonstrated significant improvement of the muscle contractility in muscles treated with hiPSCs. These results therefore provide key evidence for the therapeutic potential of human iPSCs in volumetric muscle loss injuries.
Keywords: engraftment; functional recovery; human iPSCs; innervation; muscle stem cells; satellite cells; stem cells; volumetric muscle loss (VML).
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