Pig-to-Nonhuman Primates Pancreatic Islet Xenotransplantation: An Overview

Abstract

The therapy of type 1 diabetes is an open challenging problem. The restoration of normoglycemia and insulin independence in immunosuppressed type 1 diabetic recipients of islet allotransplantation has shown the potential of a cell-based diabetes therapy. Even if successful, this approach poses a problem of scarce tissue supply. Xenotransplantation can be the answer to this limited donor availability and, among possible candidate tissues for xenotransplantation, porcine islets are the closest to a future clinical application. Xenotransplantation, with pigs as donors, offers the possibility of using healthy, living, and genetically modified islets from pathogen-free animals available in unlimited number of islets. Several studies in the pig-to-nonhuman primate model demonstrated the feasibility of successful preclinical islet xenotransplantation and have provided insights into the critical events and possible mechanisms of immune recognition and rejection of xenogeneic islet grafts. Particularly promising results in the achievement of prolonged insulin independence were obtained with newly developed, genetically modified pigs islets able to produce immunoregulatory products, using different implantation sites, and new immunotherapeutic strategies. Nonetheless, further efforts are needed to generate additional safety and efficacy data in nonhuman primate models to safely translate these findings into the clinic.

Long-Term Control of Diabetes in Immunosuppressed Nonhuman Primates (NHP) by the Transplantation of Adult Porcine Islets

“…Pig islets are an alternative source and their therapeutic potentials have been demonstrated in nonhuman primate (NHP) models as well as in rodent studies (1,2). Since relatively long-term survival of pig islets in NHPs was first demonstrated in 2006 by two independent groups (3,4), the xenotransplantation community has worked toward clinical application of pig islet xenotransplantation.…”

“…This preclinical goal, however, has been the subject of debate since it is hard to achieve in monkeys, raising the question of whether it is necessary before initiating a human clinical trial (7,8). Currently, several independent groups, including our own, have reported long-term survival of pig islets in diabetic NHPs (1,9,10), but insulin-independence for 6 months has been anecdotal, casting doubt on the translatability of this preclinical result to clinical practice.…”

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

“…10 The number of preclinical trials with porcine islets in human patients is extremely limited though porcine islets have survived and functioned for up to 6 months in nonhuman primates with immunosuppression. 11 Several preclinical trials using macroor microencapsulation of porcine islets demonstrated efficacy for several years without the need for immunosuppressants. 12 …”

Prospects of Application of Tissue-Engineered Pancreatic Constructs in the Treatment of Type 1 Diabetes

“…В той же степени близок инсу-лину человека кроличий инсулин [15]. Количество доклинических испытаний со свиными островками на людях крайне ограничено, хотя свиные островки сохранялись и функционировали в течение до 6 ме-сяцев у нечеловеческих приматов с применением иммуносупрессии [16]. Несколько доклинических испытаний с использованием макро-или микроин-капсуляции свиных островков продемонстрирова-ли, что их имплантация давала позитивный эффект в течение нескольких лет без использования имму-носупрессии [17].…”