VARIABLES IN ORGAN DONORS THAT AFFECT THE RECOVERY OF HUMAN ISLETS OF LANGERHANS1

Abstract

In an attempt to reduce the variability in the yields of human islet isolations and to identify donor factors that were potentially deleterious, we retrospectively reviewed 153 human islet isolations in our center over a 3-year period. Isolations were performed using controlled collagenase perfusion via the duct, automated dissociation, and Ficoll purification. Factors leading to successful isolations (recovery of >100,000 islet equivalents at a purity >50%) were analyzed retrospectively using univariate and multivariate analysis. Critical factors in the multiorgan cadaveric donors that were identified using univariate analysis included donor age (PPP15 min) requiring high vasopressors (>15 μg/kg/min dopamine or >5 μg/kg/min Levophed) (PPPP10 mmol/L) (OR 0.63, PPP. By donor age, success was 13% for 2.5- to 18-year-old donors (n=23), 37% for 19- to 28-year-old donors (n=30), 65% for 29- to 50-year-old donors (n=70), and 83% for 51- to 65-year-old (n=29) donors. However, when in vitro function was assessed by perifusion, the insulin secretory capabilities of islets isolated from the >50-year-old donor group was significantly reduced as compared with the 2.5- to 18-year-old group (P. Multiple regression analysis using postdigestion and postpurification islet recovery as outcome variables identified BMI, procurement team, pancreas weight, and collagenase digestion time as factors that can affect the recovery of human islets. Locally procured pancreases and donors with elevated minimum blood glucose levels were identified as factors that affect the insulin secretory capabilities of the isolated islets. This review of parameters suggests an improved approach to the prediction of successful islet isolation from human pancreas. Selection of suitable pancreases for processing may improve consistency in human islet isolation and thereby decrease costs.