2479-PUB: Mesenchymal Stromal Cells Improves Motor Function and Increases Collagen Macromolecular Organization in Muscles of Diabetic Rats

Abstract

Diabetes mellitus affects the skeletal muscle connective tissue and leads to significant physical performance impairment. The use of mesenchymal stromal cells (MSCs) is an attractive strategy to modify the microenvironment and promote tissue repair and regeneration. Male Wistar rats (225 ± 25 g) were randomly assigned to 3 groups: Control (C), Diabetic (DM) and Diabetic treated with MSCs (DM-MSCs). Diabetes was induced by Streptozotocin (50 µg/kg). Bone marrow cells were isolated from the tibia and femur. After 10 weeks of DM induction, DM-MSC rats received 4 i.p. injections of MSCs (1 x 106). Ten weeks after MSC transplantation motor performance was evaluated by Rota Rod test and the anterior tibial (TA) muscles were collected for morphometric and quantification of collagen birefringence by polarizing microscopy analysis. Statistical significance was set at 0.05. Fasting glycemia was significantly higher and body mass was significantly lower in the Diabetic (DM) and Diabetic treated with MSCs (DM + MSCs) groups compared with control group. Motor performance of the DM group (30.1 ± 9.6 s) was significantly reduced when compared to the C group (727.2 ± 92 s) and increased significantly in DM + MSCs group (786.8 ± 109.5 s). The TA muscle mass was significantly reduced in DM and DM + MSCs groups compared with C group. The muscle fiber cross sectional area followed the same pattern. The connective tissue increased in DM group compared with C group and decreased in DM + MSCs. The percentage collagen birefringence quantified in the connective tissue of the TA muscle decreased significantly in DM group when compared to C group and increased in DM + MSCs group. Motor performance was positively correlated with collagen birefringence (r = 0.83; P < 0.0001) and negatively correlated with percentage of connective tissue (r = -0.94; P < 0.0001). The results indicate that improves both motor function and the collagen macromolecular organization in type 1 DM. Disclosure G.L. Luna: None. M.A. Sabadine: None. Y. Estrada-Bonilla: None. F. Freitas Aníbal: None. Â.M. Leal: None. Funding Conselho Nacional de Desenvolvimen to Científico e Tecnológico Processo (447518/2014-3)