The effect of donor factors on human islet yield and their in vivo function

Background - A major problem in the islet field is the high selectivity exercised in accepting cadaveric pancreas for islet isolation. This practice is based on experience that indicates that islet yield and posttransplant function are related to donor demographics and injury mechanisms. Objective - To examine factors influencing islets recovery and in vivo function with emphasis on donor-related factors. Methods - Islets were isolated from 99 human donor pancreata, and islet yield was reported as islet equivalent per gram pancreatic tissue. Donor, procurement, and isolation factors were collected for each isolation and correlation statistics were performed between these variables and islet yield. Results - Results indicated a differential effect of enzyme mixes on yield with Collagenase P digestion most suitable for increased ischemic time (R² = 0.1; P < .08), Liberase with small donor pancreas size and elevated preprocurement glucose (R² = 0.15; P < .02), and Serva with female donors (R² = 0.17; P < .06). Islets from 29 isolations were further tested by transplantation under the kidney capsule of immune-deficient NOD-SCID mice. Although all 29 preparations had acceptable in vitro perfusion parameters indicating viability, only 19 functioned in vivo with serum levels of insulin >5 U/mL and C peptide >1.5 ng/mL. No significant differences in donor, procurement, and isolation factors were evident between the islet preparations that functioned in vivo and those that were nonfunctional. Conclusions - These data demonstrate that although yield is affected by a variety of donor factors and enzyme mixes, these factors do not affect islet in vivo function.