Creation of a Rich Subcutaneous Vascular Network with Implanted Adipose Tissue-Derived Stromal Cells and Adipose Tissue Enhances Subcutaneous Grafting of Islets in Diabetic Mice

Subcutaneous tissue was proposed as an optimal transplant site for islets in treatment for type I diabetes mellitus. However, vascular networks in subcutaneous tissue are too poor in their natural state to allow survive and function of the transplanted graft. This study examined whether subcutaneous implantation of adipose tissue-derived stromal cells (ADSCs) combined with minced adipose tissue could form vascular-rich beds suitable to support islet transplantation. ADSCs were isolated from male C57BL/6J mouse inguinal subcutaneous adipose tissue. ADSCs and minced adipose tissue were implanted syngeneically in subcutaneous tissue of the back of recipient mice. Four weeks later, vascularization in the implanted subcutaneous tissue was evaluated, and islets were transplanted onto the vascularized pockets. Mice that received ADSCs mixed with minced adipose tissue showed a richly vascularized pocket of tissue with significantly higher capillary density than in mice implanted with either ADSCs or minced adipose tissue only. All recipient mice of the combination ADSCs and minced adipose tissue group showed correction in blood glucose level within a week after islet transplantation and maintained normoglycemia for over 8 weeks. These mice became hyperglycemic again after removal of the subcutaneous grafts. This novel method will expand the indications for islet transplant therapy and potential clinical application of cell-based therapy.