Journal
JOURNAL OF PATHOLOGY
Volume 238, Issue 2, Pages 288-299Publisher
WILEY
DOI: 10.1002/path.4635
Keywords
pig; genetically-engineered; non-human primate; xenotransplantation; islets; organs
Funding
- National Institutes of Health (NIH) [U01 AI068642, R21 AI074844, U19 AI090959]
- University of Pittsburgh
- Revivicor Inc. (Blacksburg, VA, USA)
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI068642, U01AI091197, U19AI090959, R21AI074844] Funding Source: NIH RePORTER
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There is a critical shortage in the number of deceased human organs that become available for the purposes of clinical transplantation. This problem might be resolved by the transplantation of organs from pigs genetically engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in non-human primates (NHPs) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified, as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing five or six manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart and islet transplantation will become feasible in the near future. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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