3D cell printing of islet-laden pancreatic tissue-derived extracellular matrix bioink constructs for enhancing pancreatic functions

摘要

Type 1 diabetes mellitus (T1DM) is a form of diabetes that inhibits or halts insulin production in the pancreas. Although various therapeutic options are applied in clinical settings, not all patients are treatable with such methods due to the instability of the T1DM or the unawareness of hypoglycemia. Islet transplantation using a tissue engineering-based approach may mark a clinical significance, but finding ways to increase the function of islets in 3D constructs is a major challenge. In this study, we suggest pancreatic tissue-derived extracellular matrix as a potential candidate to recapitulate the native microenvironment in transplantable 3D pancreatic tissues. Notably, insulin secretion and the maturation of insulin-producing cells derived from human pluripotent stem cells were highly up-regulated when cultured in pdECM bioink. In addition, co-culture with human umbilical vein-derived endothelial cells decreased the central necrosis of islets under 3D culture conditions. Through the convergence of 3D cell printing technology, we validated the possibility of fabricating 3D constructs of a therapeutically applicable transplant size that can potentially be an allogeneic source of islets, such as patient-induced pluripotent stem cell-derived insulin-producing cells.