Dual Islet Transplantation Modeling of the Instant Blood‐Mediated Inflammatory Reaction. Issue 5 (19th February 2015)

• Record Type: Journal Article
• Authors: Martin, B. M.; Samy, K. P.; Lowe, M. C.; Thompson, P. W.; Cano, J.; Farris, A. B.; Song, M.; Dove, C. R.; Leopardi, F. V.; Strobert, E. A.; Jenkins, J. B.; Collins, B. H.; Larsen, C. P.; Kirk, A. D.
• Is Part Of: American journal of transplantation. Volume 15:Issue 5(2015:May)
• Page Start: 1241
• Page End: 1252
• Publication Date: 2015-02-19
• Subjects: basic (laboratory) research / science -- islet transplantation -- xenotransplantation -- animal models: porcine -- animal models: nonhuman primate -- islets of Langerhans; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13098
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract: Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood‐mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig‐to‐primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof‐of‐concept that this model can serve to properly control experiments comparing modified xenoislet preparations. WT and α1, 3‐galactosyltransferase knockout (GTKO) neonatal porcine islets were studied in nonimmunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at 1 and 24 h after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages and platelets. Insulin, complement, antibody, neutrophils, macrophages and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 h in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR. Abstract : The authors introduce a novel method for evaluating two distinct islet preparations within the same recipient, and use the model for initial studies investigating neonatal porcine islet xenografts.