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Immediate destruction of xenogeneic islets in a primate model
W Hamelmann1, D W Gray, T D Cairns
1Nuffield Department of Surgery, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Transplantation
|November 27, 1994
Summary
Xenotransplantation of rabbit islets into monkeys showed rapid graft destruction. Natural antibodies and immune cells, including neutrophils, caused hyperacute rejection, posing a significant barrier to human islet xenotransplantation.
Area of Science:
- Immunology
- Transplantation Biology
- Endocrinology
Background:
- Islet xenotransplantation offers a potential cure for diabetes.
- The risk of hyperacute rejection due to natural antibodies in islet xenografts is not well understood.
Purpose of the Study:
- To investigate the fate of rabbit islet xenografts in cynomolgus monkeys.
- To determine the role of natural antibody-mediated rejection in islet xenotransplantation.
Main Methods:
- Rabbit islets were cultured in various sera (rabbit, human, cynomolgus) in vitro.
- Islets were analyzed for immunoglobulin G (IGG) and immunoglobulin M (IGM) binding and viability.
- In vivo studies involved transplanting rabbit islets under the kidney capsule of cynomolgus monkeys.
- Graft tissues were retrieved and analyzed using light and electron microscopy.
Main Results:
- Rabbit islets demonstrated binding of both IGG and IGM heterophile antibodies.
- In vitro, islet viability decreased slowly in human or cynomolgus serum.
- In vivo, rapid graft destruction occurred within 6 hours, marked by neutrophil infiltration.
- Total graft destruction was observed within 4 days, with subsequent mononuclear cell infiltration.
Conclusions:
- Immediate rejection mechanisms, including complement and neutrophil-mediated responses, are critical barriers.
- These findings highlight significant challenges for successful human islet xenotransplantation.