A comprehensive microbiological safety approach for agarose encapsulated porcine islets intended for clinical trials

Abstract

Background: The use of porcine islets to replace insulin-producing islet β-cells, destroyed during the diabetogenic disease process, presents distinct challenges if this option is to become a therapeutic reality for the treatment of type 1 diabetes. These challenges include a thorough evaluation of the microbiological safety of the islets. In this study, we describe a robust porcine islet-screening program that provides a high level of confidence in the microbiological safety of porcine islets suitable for clinical trials.

Characterization of porcine endogenous retrovirus expression in neonatal and adult pig pancreatic islets

“…Very recently, an in vivo study evaluating the biosafety of agaroseencapsulated porcine islets used a four-checkpoint program system for microbiological evaluation. 19 This program emphasized that screening of the islet product is more likely to detect a pathological agent more reliably than in blood cells, which is supported by the updated IXA consensus statement. 4 Likewise, PERV analysis may also be more relevant in the islet product with respect to selection criteria given the lack of correlation with PERV in PBMC in this study.…”

“…18 There is also the option of rapid testing of source material for any pathogens present, while cells are in the culture environment to meet suggested criteria for pathogen evaluation. 19 It thus seems important to determine PERV status of neonatal pig islets as they are being increasingly considered as the best option to render large-scale pig-to-human islet transplantation feasible. In the present study, we quantified PERV copy number and RNA expression in islets from both neonatal and adult pigs.…”

A model for determining an effective in vivo dose of transplanted islets based on in vitro insulin secretion

“…diabetes, encapsulation, islet, transplantation, xenotransplantation added benefit of islet survival during long-term in vitro culture. The maintenance of islet viability in culture over a period of months allows not only for the comprehensive microbiological safety assessment of the macrobead, but also an evaluation of islet function prior to implant [7][8][9][10][11] . This latter feature of the porcine islet macrobead led us to examine the relationship between in vitro islet function (as measured by daily insulin secretory capacity) and in vivo graft function.…”

Xenotransplantation

“…While progress of encapsulation (micro or macro) is still under investigation [39], studies have recently been published on the use of different materials, such as agarose encapsulation, the microbiological safety of porcine islets [40], and the anti-fibrotic effect of rapamycin-containing polyethylene glycol-coated alginate microcapsules [41]. New drugs, such as cell-penetrating tat-metallothionein for immunomodulation have been studied, together with xeno-islet encapsulation [42,43].…”