Table 2.
Exploring genetic modification in donor pig islets with immune suppression regimen to increase the post-transplantation survival time.
| Type of genetic modification | Donor islets | Recipient nonhuman primates | Immune suppression regimen | MST(days) | Reference(s) |
|---|---|---|---|---|---|
| GTKO | API | Rhesus monkey | MMF + anti-CD154mAb + anti-LFA-lmAb + CTLA4-Ig | 249 | (48) |
| hCD46 | API | Cynomolgus monkey | MMF + ATG + anti-CD154mAb | >396 | (72) |
| hCD55 | Fetal | Cynomolgus monkey | Cyclosporine + steroids + cyclophosphamide or brequinar | 7 | (73) |
| GTKO/hCD55/hCD59 | NP! | Baboon | MMF + ATG + tacrolimus | 28 | (74) |
|
Multi-transgenic
(GTKO/CD46 universal expression, and beta cell-specific hTFPI/CD39/porcine CTLA4-Ig |
API | Cynomolgus monkey | MMF + ATG + anti-CD154mAb | 5 months | (75) |
| GnT-III | API | Cynomolgus monkey | None | 5 | (76) |
GTKO (galactosyltransferase gene knockout pig), hCD46 (membrane cofactor protein that controls complement activation), hCD55 (also known as hDAF; decay-accelerating factor that accelerates the decay of the C3 and C5 convertases), hCD59 (human complement regulatory protein; CRP, perturbs the complement activation cascade by inhibiting the formation of the membrane attack complex during the final stage of complement activation), hTFPI (human tissue factor pathway inhibitor; inhibits the activation of TF : FVIIa coagulation protease pathways, leading to fibrin deposition and activation of platelets during the course of hyperacute rejection), CD39 (via its ATPase activity, it decreases platelet activation and inhibits clotting), anti-LFA-1 (anti-lymphocyte function-associated antigen-1 monoclonal antibody; efficient in eliminating memory T cells).
ATG, antithymocyte globulin; CM, cynomolgus monkey; GnT-III, N-acetylglucosaminyltransferase III; MMF, mycophenolate mofetil; MTS, maximum survival time.