Influence of adipose-derived stem cell transplantation on irradiation-induced pathological changes in skeletal muscles of rabbit

Objective: To observe the pathological changes of irradiated skeletal muscles in a rabbit model after CM-Dil fluorescence-labeled adipose-derived stem cells (ASCs) transplantation and to explore the influence of ASCs on the pathological repair of radiation-induced skeletal muscle injury. Method: Unilateral hips of 64 rabbits were randomly divided into ASCs group (n = 32) and PBS group (n = 32) and they were irradiated with a single dose of 80 Gy of 9 MeV electrons beam from a linear accelerator. The non-irradiated sides with normal skeletal muscle were used as controls. 24 hours after irradiation, 1 ml of the CM-Dil fluorescence-labeled ASCs (5 × 10⁷) were locally transplanted into the irradiated side of the skeletal muscle, while PBS injection was applied as a control. 1, 4, 8 and 26 week after irradiation, 8 animals of each group were randomly executed and the tissue samples were collected. The distribution and migration of ASCs labeled by CM-Dil were observed in the frozen sections using the fluorescence microscope. The pathological changes and histological severity scoring of skeletal muscles were determined in HE staining sections. The ultrastructural changes of the muscular tissues were observed using a transmission electron microscope. Results: By fluorescence tracing, migration of ASCs along the needle passage was observed in the tissues with irradiation injury. For the ASCs group, remarkable decrease of the histological severity scores was noted at 4, 8, and 26 week after irradiation compared with those of PBS control group(U = 11.5, 12.0, 11.0, P < 0.05). The number of centronucleated regenerating myofibers in the ASCs group was significantly higher than that in the PBS group 26 week after irradiation(27.01 ± 9.36 vs. 5.23 ± 4.23, P < 0.05). Interestingly, 26 week after the irradiation, myofibrils-like structures were identified in the irradiated muscle cells after ASCs transplantation. Conclusions: ASCs transplantation could repair the radiation-induced skeletal muscle injury perhaps by promoting the compensatory hyperplasia of muscle satellite cells as well as myogenic differentiation. (authors)