Intraportal pancreatic islet cell transplantation is a successful treatment for type-1 diabetes (T1DM) in humans. Unfortunately, the lack of donor pancreatic organs is a major limitation to this therapy. As the scientific community nears towards the production of “islet like”, human derived β-cell sources; it has become increasingly evident that rigorous, pre-clinical, in vivo evaluation of such β-cell types is imperative prior to clinical trials. The gold standard large animal model for preclinical testing is the non-human primate (NHP). However, the major challenge to successful human to NHP pancreatic islet xenotransplantation is the detrimental effects of the hosts' response to transplanted foreign tissue. In particular the immediate loss of islets by the instant blood-mediated inflammatory reaction (IBMIR). In order to investigate specific parameters of immunosuppression required to protect human derived tissue from rejection in NHP, a human allo-based immunosuppressive drug regimen was tested in a cynomolgus monkey model. Intraportal human islet cell transplantation was performed into a STZ induced diabetic NHP. For one month post-transplantation, there was a significant reduction in the daily exogenous insulin requirements compared to pre-transplantation levels. Pre-transplant average insulin required: 3.85 units daily: average recorded daily blood glucose levels: 355 ± 184 mg/dL. Thirty days post transplant average insulin required: 1.03 units daily; average recorded daily blood glucose levels 196 ± 57 mg/dL. Furthermore, C-peptide was detected for up to one-month post transplantation and hemoglobin A1c levels were significantly reduced. Histological analysis of liver biopsies retrieved at 7 and 30 days post transplantation indicated varying degrees of IBMIR. However, signs of aggressive rejection or cellular infiltration were not observed. This result indicates the potential pre-clinical application of using human allo-based immunosuppressive drugs without the need for more potent drugs that are usually required for xenotransplantation in the NHP model.

CITATION INFORMATION: McGarrigle J, Bochenek M, Marchese E, Khan A, Gutierrez D, Mikalauskaite A, McCracken B, Reedy M, Omami M, Yeh C.-C, Spaggiari M, Nourmohammadzadeh M, Isa D, Ghani S, Wang L.-J, Mendoza-Elias J, Wang Y, Oberholzer J. Successful Human-to-NonHuman Primate Pancreatic Islet Intraportal Xenotransplantation Using a Human Allo-Based Immunosuppression Regimen and Its Potential Pre-Clinical Application. Am J Transplant. 2016;16 (suppl 3).

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