Integration of primary endocrine cells and supportive cells using functionalized silk promotes the formation of pre-vascularized islet-like clusters

Pancreatic islet transplantation has not yet succeeded as an overall treatment for type 1 diabetes, due to limited access to donor islets as well as low efficacy and poor reproducibility of the current procedure. Herein we describe a method to create islets-like composite clusters (co-clusters) from dispersed endocrine cells and supportive cells, with an attempt to more efficiently make use of the donor-derived material and improve compatibility with the recipient. Recombinant spider silk functionalized with cell binding motifs are used as 3D support mimicking the extracellular matrix. A cell binding motif derived from fibronectin, FN, was found superior in promoting cell adherence, while a plain RGD-motif incorporated in the repetitive part of the silk protein, 2R, increased the mobility and cluster formation of endocrine cells. Self-assembly of a mixture of FN/2R silk is utilized to integrate endocrine cells together with endothelial and mesenchymal cells into islet-like co-clusters. Both xenogenic and ...