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Chimeric pig hearts resist hyperacute rejection in ex vivo perfusion model
1Department of Surgery, University of Nebraska Medical Center, Omaha 68198-7690, USA. Tyang@unmc.edu
The Journal of Extra-Corporeal Technology
|October 30, 2001
Summary
Chimeric pig hearts, created through surrogate tolerogenesis, resist hyperacute rejection. This involves engrafting recipient immune systems into donors, preventing immune attacks on transplanted organs.
Area of Science:
- Transplantation immunology
- Xenotransplantation research
- Immunological tolerance
Background:
- Hyperacute rejection (HAR) is a major barrier in xenotransplantation.
- Surrogate tolerogenesis aims to induce immune tolerance by creating chimeric animals.
- Accommodation is a proposed mechanism for xenograft survival in tolerant recipients.
Purpose of the Study:
- To test the hypothesis that chimeric pig hearts resist hyperacute rejection.
- To evaluate the role of accommodation in xenograft survival.
- To assess the efficacy of surrogate tolerogenesis in preventing xenograft rejection.
Main Methods:
- Fetal pigs received sheep marrow infusion to create chimeric models.
- Ex vivo piglet heart perfusion model using Langendorff apparatus.
- Perfusion with plasma from sensitized and unsensitized sheep to simulate immune response.
Main Results:
- Nonchimeric hearts showed rapid deterioration with sensitized plasma (19 min).
- Chimeric hearts demonstrated prolonged function with sensitized plasma (183 min, p <.001).
- Reduced IgG, IgM deposition observed in chimeric hearts, indicating less immune attack.
Conclusions:
- Chimeric pig hearts resist hyperacute rejection mediated by antibodies and complement.
- Surrogate tolerogenesis is a viable strategy to induce tolerance in xenotransplantation.
- Accommodation plays a crucial role in the survival of chimeric xenografts.