Factors That Affect Human Islet Isolation

Abstract

More than 10,000 IEQ/kg recipient weight islets are often necessary to achieve insulin independence in patients with type 1 diabetes. Several studies have identified high BMI donor and pancreas size are important factors for the success of human islet isolation. However, donor shortage underscores the need to improve isolation outcomes from lower BMI pancreas donors and/or small pancreata. Aim of this study was to identify the critical factors affecting isolation outcome. The data from 207 isolations performed from 2002 to 2006 were analyzed with respect to donor characteristics, pancreas condition and processing variables. More than 3,000 IEQ/g pancreas weight were considered as an acceptable isolation outcome (AIO). AIO were obtained from donors with a BMI>30kg/m 2 (p=0.002). The pancreatic surface integrity was also a significant factor towards AIO (p=0.02). Moreover, a longer digestion time (p=0.04) and the proportion of trapped islet negatively affected AIO rates (p=0.004). As previously reported, pancreata from high BMI donors were suitable for islet isolation and transplantation, as they yielded higher total islet particle numbers and higher IEQ/g. Although BMI and pancreas size are not controllable due to organ donor shortage, factors such as pancreatic surface integrity, shorter digestion and lower proportions of trapped islet were found to be significant factors to obtain higher rates of AIO. The development of better protocol and systematic training of processing and procurement teams will be of assistance in increasing the number of successful human islet isolations.Islet transplantation has become a viable therapy for patients with Type 1 diabetes (1-3). However, more than one islet preparation per recipient is generally required to achieve insulin independence after transplantation and there is an urgent need to perform efficient processing to maximize both islet cell recovery and quality. Previous studies have identified donor and isolation factors affecting the outcome of islet isolation: high BMI donor and/or larger size Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access MATERIAL AND METHODS Pancreas ProcurementPancreata were obtained from heart-beating, multiorgan cadaveric donors after cerebral death for which consent for islet transplantation was given from relatives. Data collected from 207 charts and isolation records relative to pancreas processing done from January 1, 2002 through end of 2005 was retrospectively reviewed. Statistical AnalysisAll results are expressed as mean ± SE. Comparisons between groups were performed by...

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

“…Although organs donated by individuals with BMI > 25 kg/m 2 and/or age over 50 years tend to produce a greater number of islets, these islets do not always function adequately (50,51). The study by Sá and cols.…”

“…Donor characteristics (age, gender, medical history, body mass index [BMI], cause of death, use of vasopressor agents) and pancreas characteristics (size, fat content, duration of cold ischemia) may also influence the quality and quantity of the isolated islets (30,50,51). Although organs donated by individuals with BMI > 25 kg/m 2 and/or age over 50 years tend to produce a greater number of islets, these islets do not always function adequately (50,51).…”

Human islet preparations distributed for research exhibit a variety of insulin-secretory profiles

“…Human islet research uses islets from donors of different ages, sexes, BMIs, and races, that are isolated at isolation centers with different personnel and then shipped to investigators across the US. Certain donor attributes and isolation conditions may correlate with higher or lower islet yield upon isolation (19,32,37), but little is known about these potential relationships. Furthermore, how or whether to assess the health and function of health of islet preparations prior to study is not standardized.…”

Preoperative insulin secretion ability and pancreatic parenchymal thickness as useful parameters for predicting postoperative insulin secretion in patients undergoing pancreaticoduodenectomy

“…To date, however, no such preoperative parameter has been clearly identified. In human islet transplantation, a larger size or weight of the donor pancreas has been associated with a larger number of isolated islets, and pancreatic size or weight was one of the important factors for the success of islet isolation [12][13][14] suggesting that pancreatic size might directly reflect beta cell mass and insulin secretion. In recent studies, pancreatic volume measured by computed tomography (CT) with three-dimensional imaging has been correlated with glycemic control and insulin secretion [15,16].…”