Toward Maximizing the Success Rates of Human Islet Isolation: Influence of Donor and Isolation Factors

Abstract

In order to make islet transplantation a therapeutic option for patients with diabetes there is an urgent need for more efficient islet cell processing to maximize islet recovery. Improved donor management, organ recovery techniques, implementation of more stringent donor criteria, and improved islet cell processing techniques may contribute to enhance organ utilization for transplantation. We have analyzed the effects of donor and islet processing factors on the success rate of human islet cell processing for transplantation performed at a single islet cell processing center. Islet isolation outcomes improved when vasopressors, and in particular pitressin, and steroids were used for the management of multiorgan donors. Higher islet yields were obtained from adult male donors, BMI >25 kg/m 2 , adequate glycemic control during hospital stay, and when the pancreas was retrieved by a local surgical team. Successful isolations were obtained in 58% of the cases when ≥ 4 donor criteria were met, and even higher success rates (69%) were observed when considering ≥ 5 criteria. Our data suggest that a sequential, integrated approach is highly desirable to improve the success rate of islet cell processing.Key words: Pancreatic islets; Islet transplantation; Organ selection; Islet isolation; Donor management; Pancreas preservation; Pancreas recovery; Islet purification INTRODUCTION deceased donor pancreata. There is an urgent need for the definition of more stringent donor selection criteria that could help maximize the success rate of human islet Transplantation of allogeneic pancreatic islets can improve metabolic control and quality of life in patients cell processing (27,33,39,41,43,46,72). The use of regional islet cell processing centers supporting clinical with unstable type 1 diabetes (T1D) (11,13,46,47,49, 59,62). Insulin independence is generally achieved by islet transplant programs (CITP) at remote sites has proven effective in this direction (14,23). transplanting ϳ12,000 islet equivalents (IEQ)/kg of recipient body weight (11,49,59,62). Sufficient islet numIn the present study, we have analyzed the effects of donor and islet processing factors on the success rate of bers can be obtained from a single donor (11,19,62,63), but generally more than one islet preparation per recipihuman islet cell processing for transplantation performed at a single islet cell processing center. ent is required to observe insulin independence after transplantation (11,14,32,59,62). Steady progress has been obtained in recent years thanks to improved organ MATERIALS AND METHODS recovery and preservation methods (9,26,28,50), and isPancreas Procurement let isolation and purification techniques (1,22,29,52). The high islet numbers required to achieve insulin indePancreata were obtained from multiorgan, deceased donors ( (2,11,12,14). Additional organs were most of the critical steps of cell processing (namely, duct cannulation, pancreas trimming, and decision on obtained through the Texas Organ Sharing Network under an ongoing part...

Factors That Affect Human Islet Isolation

“…Previous studies have demonstrated that high BMI donors and large pancreas size are important for successful human islet isolation yielding higher islet isolation success rates (4-8), which was confirmed in our series. We found that other factors, such as pancreatic surface integrity was associated with better islet yields, pointing at the critical importance of careful pancreas recovery on the success of the islet isolation (8,9). Additionally, shorter digestion and lower proportions of trapped islet were found to be significant factors to obtain higher rates of islet yield in our study.…”

Different digestion enzymes used for human pancreatic islet isolation: A mixed treatment comparison (MTC) meta-analysis

“…The heterogeneity that we observed could originate from the improvement of islet isolation over the years, as well as differences in donor selection, enzyme batches, isolation procedures, culture medium and other reagents used for promoting islet survival. Besides that, it could also raise from differences in expertise of the isolation teams, 28,33,[39][40][41][42] and from the fact that techniques used for evaluation of SI and viability can be slightly different between studies. Regarding insulin secretion, studies used different glucose incubation time and different high and low glucose concentrations.…”

Experience of islet isolation without neutral protease supplementation

“…18 It should be noted, however, that other studies failed to show clear associations between CIT and islet isolation success. [19][20][21] Possible approaches to improve islet yield from ischemically damaged pancreata may shed some light on this disagreement. For pancreas with prolonged CIT which Figure 1.…”