Effects of adipose-derived stem cell transplantation on radiation-induced skeletal muscle fibrosis in rabbits

Abstract

Objective To investigate the effects of adipose-derived stem cell (ASC) transplantation on radiation-induced skeletal muscle fibrosis in New Zealand rabbits. Methods Totally 64 rabbits were irradiated at unilateral hip with a single dose of 80 Gy of 9 MeV electrons generated from a linear accelerator and then were randomly divided into ASCs group and PBS group with 32 abbits in each group. The non-irradiated side with normal skeletal muscle was used as control. At 24 after irradiation, 1 ml PBS containing 5×107ASCs labbed with CM-Dil or 1 ml PBS was injected into the skeletal muscle in the irradiated side of these two groups, respectively. At 1, 4, 8 and 26 weeks after irradiation, the skeletal muscles of 8 rabbits in each group were collected. Masson staining was used to evaluate the level of skeletal muscle fibrosis. The expression of transforming growth factor β1(TGF-β1) in the skeletal muscle tissues was evaluated by immunohistochemical method (IHC) and Western blot. Results The fluorescence tracing method showed that ASCs could migrate in the injured muscle and fibrosis was more serious in the PBS group. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than that of PBS groups at 4, 8 and 26 weeks after irradiation(t=4.62, 5.99, 10.48, P <0.05). The expression level of TGF-β1 protein in the ASCs group was significantly lower than that in the PBS groups at 4, 8 and 26 weeks after irradiation(t=3.79, 16.45, 15.17, P<0.05). Conclusions ASC transplantation could alleviate radiation fibrosis by down-regulating the level of TGF- β1 protein in the irradiated skeletal muscle. Key words: Adipose-derived stem cells; Skeletal muscle; Radiation fibrosis; TGF-β1; Rabbit model