Combining Donor Characteristics with Immunohistological Data Improves the Prediction of Islet Isolation Success

Abstract

Variability of pancreatic donors may significantly impact the success of islet isolation. The aim of this study was to evaluate donor factors associated with isolation failure and to investigate whether immunohistology could contribute to organ selection. Donor characteristics were evaluated for both successful (n = 61) and failed (n = 98) islet isolations. Samples of donor pancreatic tissue (n = 78) were taken for immunohistochemical examination. Islet isolations with 250000 islet equivalents were considered successful. We confirmed that BMI of less than 25 kg/m2 (P < 0.001), cold ischemia time more than 8 hours (P < 0.01), hospitalization longer than 96 hours (P < 0.05), higher catecholamine doses (P < 0.05), and edematous pancreases (P < 0.01) all unfavorably affected isolation outcome. Subsequent immunohistochemical examination of donor pancreases confirmed significant differences in insulin-positive areas (P < 0.001). ROC analyses then established that the insulin-positive area in the pancreas could be used to predict the likely success of islet isolation (P < 0.001). At the optimal cutoff point (>1.02%), sensitivity and specificity were 89% and 76%, respectively. To conclude, while the insulin-positive area, determined preislet isolation, as a single variable, is sufficient to predict isolation outcome and helps to improve the success of this procedure, its combination with the established donor scoring system might further improve organ selection.

Pancreatic beta cell/islet mass and body mass index

“…It is recognized that islet isolation from young donors results in lower recovery with difficulty in separating islets from exocrine tissues by collagenase digestion, regardless of BMI unlike adult donors. [28][29][30][31] In fact, donors under 20 years of age are listed as an unfavorable factor under NAIDS, although it has been demonstrated that islets from young donors exhibit superior function in insulin secretion. 32,33 It is suggested that there are unique ECM components/structure in the pancreas of the young.…”

The long noncoding RNA MALAT1 predicts human islet isolation quality

“…A recent study demonstrated the potential of assessing insulin immunopositive area in predicting islet isolation outcomes with 89% sensitivity and 76% specificity (29). Our data demonstrate that MALAT1 expression alone (AUC: 0.83, maximum specificity of 100% and a sensitivity of 80%) or along with Edmonton Donor Points, BMI, and NAIDS can accurately stratify a donor pancreas to group 1 (transplantable) or group 3 (not transplantable) before the initiation of islet isolation.…”

Regulation of Inflammatory Response in Islet Transplantation

“…Pancreas procurement initiates ischemia [4,5] and cold ischemic time (CIT) beyond 8 hours results in reduced islet yields [6], poor purification recovery [7] and graft dysfunction in human islet transplantation [8,9]. Cold ischemia time is not of major concern in autologous islet transplantation, as most centers have islet isolation facility for processing the pancreas.…”