Skip to main content
. 2023 May 3;53(6):351–366. doi: 10.4070/kcj.2022.0351

Table 2. Key obstacles of cross-species heart transplantation and solutions.

Obstacles and mechanism Solution
Hyperacute rejection
Porcine carbohydrate antigens - Knock-out of responsible enzymes: GGTA1, β4GalNT2, and CMAH
Complement cascade - Transgenic expression of human CD55 (DAF) and CD46 (membrane cofactor protein)
Coagulation abnormality - Transgenic expression of human TBM and EPCR
Antibody mediated rejection
T-cell dependent antibody production by activated B-cells - CD40-CD40L co-stimulation blockade using anti-CD40 antibody
Cellular rejection
B-cell and T-cell activation - B- and T-cell depletion at induction
- Immunosuppressant
Macrophage activation - Transgenic expression of human CD47
Post-transplantation management
Perioperative cardiac xenograft dysfunction - Non-ischemic continuous preservation
Post-transplantation xenograft growth - Strict blood pressure control
- Early steroid tapering
- mTOR inhibitor administration
- Growth hormone receptor knockout
Zoonotic viral transmission
PERV - PERV polymerase knockout pigs

CMAH = N-acetylneuraminic acid hydroxylase; DAF = decay accelerating factor; EPCR = endothelial protein C receptor; GGTA1 = α1,3-galactosyltransferase; PERV = porcine endogenous retrovirus; mTOR = mammalian target of rapamycin; TBM = thrombomodulin; β4GalNT2 = β1,4-N-acetylgalactosyltransferase.