Islet transplantation into the portal vein is currently regarded as the most promising therapeutic approach for reversing Type-1 diabetes. Nevertheless, islet loss due to inflammatory reaction, hypoxia, and peri-islet thrombosis, often hinders sustained insulin independence in most patients, despite the considerable number of islets utilized. In response to these constraints, we are focused on the development of an acellular biological vascular graft with an outer layer coated with an islet-populated hydrogel known as the Biovascular Pancreas or “BVP” (Fig. 1 A). When connected to arterial circulation, the BVP provides an oxygen-rich environment for the embedded islets due to blood flow through the BVP lumen. Previously, we demonstrated that the BVP can restore normoglycemia in diabetic rodent models with islet numbers as low as 1500 islet IEQ per rat. Recently, we generated BVPs made of 6-mm inner-diameter human acellular vessels (HAV) that are coated with a primate islet-populated fibrin layer and tested the islet engraftment in non-human primates. When implanted as an aortic bypass graft in a Cynomolgus macaque for two weeks, the BVP supported islet viability and insulin secretion (Fig. 1 B, C and D). Our results demonstrate the first primate implantation of the BVP and its potential to improve transplanted islet viability which will be evaluated via subsequent long-term in vivo studies.
M.H. Kural: None. K.M. Nash: Employee; Humacyte Inc. K.M. Naegeli: Employee; Humacyte Global, Inc. Stock/Shareholder; Humacyte Global, Inc. H. Qian: None. J. Wang: None. R.D. Kirkton: Employee; Humacyte, Inc. L.E. Niklason: None.
JDRF Industry Discovery and Development Partnership (IDDP) (3-IND-2023-1380-I-X)
