Successful Islet Transplantation from Nonheartbeating Donor Pancreata Using Modified Ricordi Islet Isolation Method

TLDR

Current success of islet transplantation has led to donor shortages, creating a need to use marginal donors to alleviate the deficit. The study aimed to enhance islet transplantation efficacy by employing non‑heart‑beating donors (NHBDs). Using a modified Ricordi protocol, the authors applied ductal trypsin‑inhibitor injection, ET‑Kyoto preservation, and iodixanol purification to improve islet isolation from both porcine and human pancreata. The protocol produced an average of 399,469 ± 36,411 islet equivalents per pancreas, with 85 % transplanted into six type 1 diabetic patients who all began insulin secretion, achieved HbA1c reductions from 7.5 % to 5.1 %, lowered insulin needs from 49.2 to 11 units, and one patient became insulin‑free, demonstrating the feasibility of NHBD islet transplantation.

Abstract

Current success of islet transplantation has led to donor shortage and the need for marginal donor utilization to alleviate this shortage. The goal of this study was to improve the efficacy of islet transplantation using nonheartbeating donors (NHBDs).First, we used porcine pancreata for the implementation of several strategies and applied to human pancreata. These strategies included ductal injection with trypsin inhibitor for protection of pancreatic ducts, ET-Kyoto solution for pancreas preservation, and Iodixanol for islet purification.These strategies significantly improved both porcine and human islet isolation efficacy. Average 399,469+/-36,411 IE human islets were obtained from NHBDs (n=13). All islet preparations met transplantation criteria and 11 out of 13 cases (85%) were transplanted into six type 1 diabetic patients for the first time in Japan. All islets started to secrete insulin and all patients showed better blood glucose control without hypoglycemic loss of consciousness. The average HbA1c levels of the six recipients significantly improved from 7.5+/-0.4% at transplant to 5.1+/-0.2% currently (P<0.0003). The average insulin amounts of the six recipients significantly reduced from 49.2+/-3.3 units at transplant to 11+/-4.4 units (P<0.0005) and five out of six patients reduced to less than half dose. The first patient is now insulin free, the first such case in Japan.This demonstrates that our current protocol makes it feasible to use NHBDs for islet transplant into type 1 diabetic patients efficiently.