Sustained Release of Stromal Cell-Derived Factor-1α from Injectable Hydrogels in Combination with Endothelial Progenitor Cells Effectively Promotes Neovascularization in Ischemic Diabetic Rats

Objective: To investigate whether sustained release of stromal cell-derived factor-1 alpha (SDF-1 alpha) from injectable hydrogel (Gel) along with endothelial progenitor cells (EPCs) might act synergistically on therapeutic neovascularization in diabetes. Methods: EPCs were isolated and cultured from the bone marrow of rats. SDF-1 alpha was encapsulated in thermal-sensitive Gel during the formation of the Gel and then injected into diabetic rats with unilateral hindlimb ischemia rats accompanied with EPCs. SDF-1 alpha was released along with degradation of Gel. Migration activity of EPC was investigated using a transwell chamber assay. Capillary density was measured after testing the plasma level of SDF-1 alpha and vascular endothelial growth factor (VEGF) to evaluate the neovascularization. Results: Migration activity of EPC was enhanced in a concentration-dependentmanner, and the concentration of SDF-1 alpha of 80 mu g/L was chosen in the following experiment. The number of CXCR4+ EPCs and the plasma levels of SDF-1 alpha and VEGF was increased after the delivery of SDF-1 alpha or EPC. Furthermore, most satisfactory results were obtained in the EPCs plus SDF-1 alpha group. Meanwhile, capillary density in the Gel-SDF-1 alpha-EPC group was also significantly higher as compared with the other groups. Conclusion: The combination of sustained release of SDF-1 alpha and EPCs enhanced neovascularization in ischemic diabetic rats, which is potentially a novel and efficient approach in the treatment of diabetic ischemic diseases.