Heterogeneity of Human Pancreatic Islet Isolation Around Europe: Results of a Survey Study

Abstract

Background. Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries. Methods. A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan. Results. Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities. Conclusions. The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution

“…However, since beta cell recovery after culture may be influenced by many confounders [22,25,26], the measurement of beta cells after purification was used to examine if DCD III organs are suitable for the preparation of islet cell grafts. Islet mass serves since long as a criterium to select pancreatic islet isolates for clinical transplantation [1,6,15]. It is usually determined as the number of IEQ after dithizone staining [27].…”

“…Since the intensity of this staining decreases during culture in absence of a loss of viable beta cells, we have replaced it by a count of beta cells, which, in addition, is a direct assessment of the active component in the grafts. We, and others, do not perform functional beta cell assays on each isolate [15]. This is not to deny the importance of the functional state of the prepared beta cell mass for its therapeutic use; it reflects the lack of time to add the data of this analysis to the selection process [6].…”

“…In general, DCD III organs exhibit a higher risk for posttransplant dysfunction due to an initial period of warm ischemia before starting cold preservation [12][13][14]. This risk discourages islet transplant programs to include DCD III organs for islet isolation or to use more stringent selection criteria then for donors after brain death (DBD) [15], despite previously reported comparisons between pancreases procured from DCD III and DBD that were indicative for a similar yield in isolated islets [10,11,16,17]. While these DCD III cohorts were small and highly selected, the present study is conducted on a larger, more heterogenous series and directly determines the target criterium, the number of beta cells, and its correlation with donor and procurement variables.…”

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update

“…Islets have not been classified as drugs (Advanced Technology Medicinal Products in Europe) and have not been subject to marketing authorization requirement (Figure 2B). Islets are still processed in special laboratories (i.e., GMP facilities) designed for aseptic cell product processing borrowed from the Good Manufacture Practice (GMP) regulations (Table 1; 20) 25 . Clinical safety and efficacy outcomes have remained excellent for allo‐ITx performed in accredited transplant centers worldwide (Table S1C) 21,26,27 .…”

Pancreas and Islet Cell Transplantation

“…Indeed, the complexity, cost, and regulatory requirements for clinical human islet isolation and transplantation have stimulated the establishment of several islet transplant networks within Europe and the USA. Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are achieving good outcomes as a result of standardization of islet cell product isolation (Nano et al 2019). Although human islet transplantation has been established as a valid and safe treatment for patients with type 1 diabetes, the utilization rates of human pancreases for clinical islet transplantation are still limited and substantially determined by the quality and composition of collagenase blends (Brandhorst et al 2019).…”