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.