Islet transplantation in the discordant tilapia-to-mouse model: a novel application of alginate microencapsulation in the study of xenograft rejection

Abstract

Our results indicate that rejection in the tilapia-to-mouse model follows a pattern similar to other models of discordant islet cell xenotransplantation.

Reversal of diabetes in non‐immunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection

“…Previous studies in murine models collectively suggested that islet xenograft rejection is initiated, mediated, and dominated primarily by major histocompatibility complex (MHC) class II restricted CD4 + T cells; those T cells are activated through indirect recognition of processed SLA class I xenoantigens presented by host antigen‐presenting cells [41–43]. Those activated, xenoreactive CD4 + T cells are critical effectors in the xenorejection process [44,45] and provide the necessary signals for growth and maturation of additional effector mechanisms involving, first and foremost, macrophages [40,46]. The dominant involvement of macrophages in the effector phase of islet xenograft rejection accounts for its unique properties, strength, and complexity and calls for tailored interventions [22,40,46].…”

Biocompatibility and function of microencapsulated pancreatic islets

“…A second layer that consists of alginate is applied for coverage of the unbound poly-L-lysine group [5]. Allotransplantation of microencapsulated islets in experimental animals has been extensively studied [6][7][8] while not so many studies have been published on discordant xenotransplantation [3,9]. The implantation of encapsulated islets reversed diabetes in xenotransplantation models, but the continuing function of the implants usually required immunosuppression and often generated Wbrotic reactions.…”

Ancestral genomic duplication of the insulin gene in tilapia: An analysis of possible implications for clinical islet xenotransplantation using donor islets from transgenic tilapia expressing a humanized insulin gene

“…3,6,7 Rejection of tilapia BBs in euthymic murine recipients is CD4 T-cell dependent and mechanistically similar to that of porcine islet xenografts. 8 However, unlike porcine and most other mammalian islets, tilapia are too phylogenetically primitive for their islets to express the dominant xenoantigen, a(1,3)Gal. 9 Because of the low metabolic needs of tilapia (n.b., tilapia are evolved to thrive in warm stagnant water nearly devoid of dissolved oxygen), tilapia BBs are an order of magnitude more hypoxia resistant than mammalian islets 10 making them ideal for survival and long-term function within encapsulation devices 11 which can be further prolonged when combined with co-stimulatory blockade.…”