The usefulness and limitations of the diabetic macaque model in evaluating long‐term porcine islet xenograft survival

Abstract

THE model-induced confounding described interferes with accurate interpretation of safety and efficacy studies, which affects the translational value of pig-to-NHP islet cell transplant studies to the pig-to-human transplant condition.

Virus safety of islet cell transplantation from transgenic pigs to marmosets

“…However, in the case of islet cell transplantation, there is an ongoing discussion on the usefulness and limitations of the non-human primate model for this evaluation (Graham et al, 2011;Graham and Schuurman, 2013;Wijkstrom et al, 2013;Cooper et al, 2013;Denner and Graham, 2015). Concerning islet cell transplantation there are two major limitations: First, the differences in glucose metabolism between humans and pigs on one side, and non-human primates on the other, are obvious.…”

Validity of animal models of type 1 diabetes, and strategies to enhance their utility in translational research

“…There are also differences in the metabolic demand between rodents, pigs, NHPs, and humans that should be considered when designing dose strategies for β-cell replacement therapies, and also when defining outcomes of success in various models. This has been observed for pig xenotransplantation cell therapy products where the much higher need for insulin in macaques (than in humans or pigs) creates an imbalance between the metabolic demand and the pig islet product; this situation is model-specific and is not anticipated in the clinical condition (Casu et al, 2008;Graham et al, 2011a;Graham and Schuurman, 2013;Wijkstrom et al, 2013). Dosing adaptations may be one way to successfully compensate this effect in short-term preclinical studies: this adaptation obviously lacks translational value (Lee et al, 2013a).…”

Recent Advances in Cell Replacement Therapies for the Treatment of Type 1 Diabetes

“…Not only was pig insulin previously used to treat diabetic patients prior to the production of recombinant human (rh) insulin (37), but porcine glucose physiology is not too dissimilar from that of humans, indicating their functional compatibility (6,38). Pigs can also be bred for this specific purpose, creating a large, readily available source of islets.…”