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.