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Immunologic Rejection

Within minutes after pig-to-human heart xenotransplantation, hyper-acute rejection might occur, resulting in an acute injury to the vascular endothelial cells of the donor organ. Xenoractive antibodies and the complement system appear to be the two primary factors that mediate HAR.

 

Approaches that will prevent HAR include genetically modified pigs and expression of human complement regulatory proteins in the pig.


  •  According to studies on immunologic rejection, many genetically engineered pigs were generated to overcome molecular incompatibilities. Eliminating the gene coding for the enzyme a(1-3) will result in the absence of an a(1-3)-Gal epitope in the pig and could significantly decrease the risk of HAR. 
  • Pigs and humans exhibit similar human complement regulatory proteins (CRPs), but pig CRPs are not enough to protect pig cells from human complement-mediated injury. Human CRPs (hCRPs) can be introduced to pig cells to inhibit human complement-mediated injury. Researchers have also indicated that expressing human CRPs can also extend xenograft survival time. 




Citation:  

Boneva, R. (2009, July 8). Xenotransplantation and risks of zoonotic infections. Retrieved from Taylor and Francis Online : https://www.tandfonline.com/doi/abs/10.1080/07853890410018826

McMains, V. (2022, March 2). Institute of Human Virology's infectious disease experts perform pathogen surveillance for unprecedented pig-to-human heart transplant at University of Maryland Medical Center. 2022 Archives | University of Maryland School of Medicine. Retrieved February 27, 2023, from https://www.ihv.org/news/2022-News/Institute-of-Human-Virologys-Infectious-Disease-Experts-Perform-Pathogen-Surveillance-for-Unprecedented-Pig-to-Human-Heart-Transplant-at-University-of-Maryland-Medical-Center.html 






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