Boosting the engraftment of subcutaneously transplanted pancreatic islets by nanofat

Aims: In the therapy of type 1 diabetes mellitus, the subcutaneous space has been suggested to be a clinically preferable transplantation site for pancreatic islets due to its easy accessibility. However, its poor vascularisation capacity and, thus, challenging environment typically result in islet engraftment failure. In the present proof-of-principle study, we demonstrate that this problem can be overcome by nanofat, an emulsified fat derivative already used in clinical practice. Materials and methods: The cellular composition of nanofat was assessed by immunohistochemistry. The angiogenic activity of the soluble and cellular nanofat fraction was analyzed by an angiogenic protein array, tube formation and spheroid sprouting assays. The viability and endocrine function of islets exposed to the nanofat fractions was investigated by flow cytometry, qRT-PCR and ELISA. In vivo, islets and nanofat were co-transplanted under the kidney capsule as well as into the subcutaneous space of diabetic animals. Results: In a panel of in vitro assays, we showed that the soluble and cellular nanofat fraction improve the viability, hormone release, and angiogenic activity of islets. The beneficial effects of these two fractions were validated in vivo in the murine diabetic kidney capsule model, as indicated by an accelerated restoration of normoglycaemia. The co-transplantation of islets with nanofat resulted in successful islet engraftment within the subcutaneous space of diabetic mice. Conclusions: These findings demonstrate that nanofat markedly boosts the vascularisation and endocrine function of islet grafts. Hence, its co-transplantation with pancreatic islets represents a simple, clinically feasible approach to make the subcutaneous space available for future islet transplantation.