Mesenchymal stem cell-conditioned medium facilitates angiogenesis and fracture healing in diabetic rats.

The most critical factor for fracture union is the blood supply to the fracture site, which is usually impaired in patients with diabetes. Recently, mesenchymal stem cells-derived conditioned medium (MSC-CM) has shown significantly higher levels of angiogenic factors, such as VEGF and IL-6. We demonstrate in this report that MSC-CM delivered in gelatin sponges stimulates angiogenesis and promotes fracture healing in a diabetic rat model. Subcutaneous implantation of gelatin sponges soaked in MSC-CM demonstrated better tissue ingrowth and higher capillary densities at 2 and 3 weeks than gelatin sponges in minimal essential medium (MEM) or 293 cell-derived conditioned medium (293-CM). Implantation of fibular defects with gelatin sponges soaked in MSC-CM enhanced bone ingrowth and fracture healing rates compared to 293-CM and MEM groups at 8 weeks. Micro-computed tomography analysis further indicated a higher new bone volume in the MSC-CM group compared to the other diabetic groups. Histological analysis with CD31 immunostaining also revealed that MSC-CM increased endothelial cell counts compared to the other groups. Together, these results indicated that gelatin sponges used to deliver MSC-CM promote angiogenesis and fracture healing in a diabetic model and may be an alternative strategy for treating fracture non-union in patients with diabetes.