Can We Re-Engineer the Endocrine Pancreas?

Engineering endocrine pancreatic tissue is an emerging topic in type 1 diabetes with the intent to overcome the current limitation of β cell transplantation. During islet isolation, the vascularized structure and surrounding extracellular matrix (ECM) are completely disrupted. Once implanted, islets slowly engraft and mostly are lost for the initial avascular phase. This review discusses the main building blocks required to engineer the endocrine pancreas: (i) islet niche ECM, (ii) islet niche vascular network, and (iii) new available sources of endocrine cells.

Current approaches include the following: tissue engineering of endocrine grafts by seeding of native or synthetic ECM scaffolds with human islets, vascularization of native or synthetic ECM prior to implantation, vascular functionalization of ECM structures to enhance angiogenesis after implantation, generation of engineered animals as human organ donors, and embryonic and pluripotent stem cell-derived endocrine cells that may be encapsulated or genetically engineered to be immunotolerated. Substantial technological improvements have been made to regenerate or engineer endocrine pancreatic tissue; however, significant hurdles remain, and more research is needed to develop a technology to integrate all components of viable endocrine tissue for clinical application.