Journal article
Control of IBMIR in neonatal porcine islet xenotransplantation in baboons
WJ Hawthorne, EJ Salvaris, P Phillips, J Hawkes, D Liuwantara, H Burns, H Barlow, AB Stewart, SB Peirce, M Hu, AM Lew, SC Robson, MB Nottle, AJF D'Apice, PJ O'Connell, PJ Cowan
American Journal of Transplantation | Published : 2014
DOI: 10.1111/ajt.12722
Abstract
The instant blood-mediated inflammatory reaction (IBMIR) is a major obstacle to the engraftment of intraportal pig islet xenografts in primates. Higher expression of the galactose-α1,3-galactose (αGal) xenoantigen on neonatal islet cell clusters (NICC) than on adult pig islets may provoke a stronger reaction, but this has not been tested in the baboon model. Here, we report that WT pig NICC xenografts triggered profound IBMIR in baboons, with intravascular clotting and graft destruction occurring within hours, which was not prevented by anti-thrombin treatment. In contrast, IBMIR was minimal when recipients were immunosuppressed with a clinically relevant protocol and transplanted with NICC ..
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Funding Acknowledgements
The authors wish to thank the staff of the Australian National Baboon Colony, in particular Scott Heffernan, Dr. Penny Farrell and Professor Annemarie Hennessy, for their ongoing support of this project. We thank Matt Borg for his dedicated care of the pigs used in this study and Dr. Ross Matthews for veterinary supervision. We also thank staff of the Experimental Medical Surgical Unit, St. Vincent's Hospital, Melbourne, for their assistance. We thank GTC Biotherapeutics Corporation (Framingham, MA) for the donation of recombinant human anti-thrombin. This work was supported by the National Health and Medical Research Council of Australia and the Juvenile Diabetes Research Foundation.