Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth

Curr Cardiol Rep. 2023 Nov;25(11):1649-1656. doi: 10.1007/s11886-023-01978-4. Epub 2023 Nov 8.

Abstract

Purpose of review: The first successful pig to human cardiac xenotransplantation in January 2022 represented a major step forward in the fields of heart failure, immunology, and applied genetic engineering, using a 10-gene edited (GE) pig. This review summarizes the evolution of preclinical modelling data which informed the use of each of the 10 genes modified in the 10-GE pig: GGTA1, Β4GalNT2, CMAH, CD46, CD55, TBM, EPCR, CD47, HO-1, and growth hormone receptor.

Recent findings: The translation of the 10-GE pig from preclinical modelling to clinical compassionate xenotransplant use was the culmination of decades of research combating rejection, coagulopathy, inflammation, and excessive xenograft growth. Understanding these 10 genes with a view to their combinatorial effects will be useful in anticipated xenotransplant clinical trials.

Keywords: Cardiac xenotransplantation; Coagulopathy; Genetic engineering; Growth hormone; Inflammation; Rejection.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blood Coagulation Disorders*
  • Genetic Engineering
  • Graft Rejection* / genetics
  • Graft Rejection* / prevention & control
  • Humans
  • Inflammation
  • Swine
  • Transplantation, Heterologous