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Complement activation, its consequences, and blockade by gene transfer

C A Carrington1, A C Richards, J van den Bogaerde

  • 1Imutran Ltd., Novartis Pharma AG Company, Cambridge, UK.

World Journal of Surgery
|November 15, 1997
PubMed
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Transplanting pig organs into humans faces hyperacute rejection (HAR) due to immune response. Genetically modifying pigs to express human complement regulators prevents HAR, enabling further xenotransplantation research.

Area of Science:

  • Xenotransplantation
  • Immunology
  • Genetics

Background:

  • Xenotransplantation of pig organs is hindered by hyperacute rejection (HAR).
  • HAR is caused by antibodies attacking pig organs, activating the complement system.
  • Pig complement regulatory proteins are ineffective against human complement.

Purpose of the Study:

  • To overcome hyperacute rejection in pig-to-human xenotransplantation.
  • To investigate the efficacy of expressing human complement regulatory proteins (RCAs) in pigs.

Main Methods:

  • Genetically engineering pigs to express human RCAs.
  • In vitro testing of pig endothelial cells expressing human RCAs.
  • Ex vivo perfusion studies using pig organs and human blood.

Related Experiment Videos

  • Primate model studies of xenografts from transgenic pigs.

    • Main Results:

    • Pig endothelial cells expressing human RCAs showed resistance to human complement.
    • Transgenic pigs expressing human RCAs demonstrated improved organ function and survival in ex vivo and primate studies.
    • Expression of human RCAs effectively prevented hyperacute rejection.

    Conclusions:

    • Genetic incorporation of human RCAs into pigs overcomes the primary immunological barrier of HAR.
    • This advancement allows for the study of subsequent xenograft rejection mechanisms in pig-to-human transplantation.