Preconditioning with SDF-1 improves therapeutic outcomes of bone-marrow-derived mesenchymal stromal cells in a mouse model of STZ-induced diabetes

IntroductionNumerous experimental studies have suggested that bone marrow stem cells (BMSCs) ameliorate diabetes in animal models. But a number of critical obstacles lie ahead of this new strategy including reducing stem cell homing to the damaged tissue. The present study to investigate whether preconditioning of BMSCs with stromal derived factor 1α (SDF-1α) could enhance their homing to the pancreas and promote regeneration of the pancreatic β cells after being intravenously injected.MethodsThe BMSCs were isolated by flushing method and identification of the cells was done by flow cytometry for CD73+, CD90+, CD34-and CD45- markers. On 10 days after STZ induction of diabetes, BMSCs or BMSCs+SDF1α at a dose of 1×106 cells/1 ml PBS were transplanted via the tail vein. The same volume of PBS (1 ml) was injected as a vehicle. 48 hours after transplantation, homing of BMSCs were analysis by flow cytometry and fluorescent microscope. At 30 days after the cell transplantation, blood and pancreatic tissue samples were taken from all mice for biochemical and histological studies.ResultsBMSCs+SDF-1α had a high ability of homing into the injured pancreas (P ≤ 0.05 vs. BMSCs). The BMSCs+SDF-1α group showed further differentiation into insulin secreting βcells (P ≤ 0.05 vs. BMSCs). Transplantation of BMSCs+SDF-1α significantly reduced blood glucose level (P ≤ 0.05 vs. BMSCs).ConclusionOur results showed the effectiveness of SDF-1 preconditioning in BMSCs transplantation of STZ-induced diabetes mice, might be achieved through improvement of BMSCs homing into the injured pancreas

کلیدواژه ها:

Diabetes mellitus ، Transplantation ، Bone marrow stem cells ، Stromal derived factor 1α