Embryonic Stem Cell-derived Mesenchymal Stem Cells Alleviate Skeletal Muscle Injury Induced by Acute Compartment Syndrome

Abstract

Background Acute compartment syndrome (ACS), a well-known complication of musculoskeletal injury, results in muscle necrosis and cell death. Embryonic stem cell-derived mesenchymal stem cells (ES-MSCs) have been shown to be a promising therapy for ACS. However, their effectiveness and potentially protective mechanism remain unknown. The present study was designed to investigate the efficacy and underlying mechanism of ES-MSCs in ACS-induced skeletal muscle injury. Method A total of 120 male Sprague–Dawley (SD) rats underwent 2 hours of intracompartmental pressure elevation by saline infusion into the anterior compartment of the left hindlimb to establish the ACS model. ES-MSCs were differentiated from the human embryonic stem cell (ES) line H9. A dose of 1.2×106 of ES-MSCs was intravenously injected during fasciotomy. Post-ACS assessments included skeletal edema index, serum indicators, histological analysis, apoptosis, fibrosis, regeneration, and functional recovery of skeletal muscle. Then, fluorescence microscopy was used to observe the distribution of labeled ES-MSCs in vivo, and western blotting and immunofluorescence analyses were performed to examine M2 macrophage infiltration in skeletal muscle. Finally, we used liposomal clodronate to deplete macrophages and reassess skeletal muscle injury in response to ES-MSC therapy. Result ES-MSCs significantly reduced systemic inflammatory responses, ACS-induced skeletal muscle edema and cell apoptosis. In addition, ES-MSCs inhibited skeletal muscle fibrosis and increased regeneration and functional recovery of skeletal muscle after ACS. The beneficial effects of ES-MSCs on ACS-induced skeletal muscle injury were accompanied by an increase in CD206-positive M2 macrophage polarization. After depleting macrophages with liposomal clodronate, the beneficial effects of ES-MSCs were abolished. Conclusion Our findings suggest that embryonic stem cell-derived mesenchymal stem cells infusion could effectively alleviate ACS-induced skeletal muscle injury, in which the protective effects were related to M2 macrophage polarization.

Radioprotective countermeasures for radiation injury (Review)

“…For radiation-shock trauma, stem cells have been shown to enhance the response of the body to infection and improve chronic diseases, such as osteomyelitis and osteoarthritis that radiation-shock trauma can induce (140). In addition, compartment syndrome and segmental bone defects can also be treated with stem cell transplantation (141,142).…”