Stromal cell-derived factor-1 promotes bone marrow mesenchymal stem cells proliferation, survival and bone morphogenetic protein-6 expression in diabetic mice

Abstract

Background: Bone marrow mesenchymal stem cells (BMSCs) transplantation holds promise for treating type 1 diabetes (T1DM) and its complications. Stromal cell-derived factor-1 (SDF-1) is implicated in stem cell homing and survival, yet its role in modulating BMSCs function in the context of diabetes remains unclear. Objectives: This study aimed to investigate whether pretreatment with SDF-1 enhances the proliferation, survival and paracrine function of BMSCs and to evaluate its therapeutic effects on hyperglycemia and bone loss in a streptozotocin (STZ)-induced diabetic mouse model. Methods: Mouse BMSCs were pretreated with SDF-1 (10 ng/ml) for 24 hours. Cell proliferation, apoptosis and BMP-6 expression were assessed in vitro. Diabetic mice were induced with STZ and treated via tail vein with untreated BMSCs or SDF-1-pretreated BMSCs. Body weight, blood glucose, bone mineral density, serum BMP-6 and pancreatic Bcl-2 expression were analyzed. Results: SDF-1 pretreatment significantly promoted BMSCs proliferation, inhibited apoptosis and upregulated BMP-6 expression in vitro. In diabetic mice, transplantation of BMSCs improved hyperglycemia, weight gain, BMD and upregulated Bcl-2. These therapeutic effects were significantly enhanced when BMSCs were pretreated with SDF-1 (P < 0.05). Conclusion: SDF-1 stimulates BMSCs proliferation, reduces apoptosis and upregulates BMP-6 expression, thereby improving hyperglycemia and bone loss in diabetic mice. These effects suggest a potential role for SDF-1 in enhancing the therapeutic efficacy of BMSCs, possibly through promoting their survival and osteogenic paracrine function.