Table 1. Preclinical experience of porcine islet xenotransplantation in diabetic nonhuman primates.
Immunosuppression that is not currently available for human use has been highlighted. All but one study with considerably prolonged survival (>100 days) use at least 4 agents.
| Porcine donor | Recipient species | Transplant Site | Immunosuppression | Maximum graft survival | Reference |
|---|---|---|---|---|---|
| Adult | Baboon (n=3) | Intraportal | ATG +Cyclosporine+Aza | <2 days | Buhler et al.7 |
| Adult | Rhesus (n=6) | Intraportal | None | >3 days | Kirchhof et al.8 |
| Adult | Cyno (n=12) | Intraportal | Group I: anti-IL-2R, FTY720, everolimus, anti-CD154 Group II: anti-IL-2R, FTY720, everolimus, anti-CD154 Group III: anti-IL-2R, FTY720, everolimus, anti-CD154, leflunomide |
45 days >187 days >158 days |
Hering et al.10 |
| Neonatal | Rhesus (n=9) | Intraportal | Group I: no immunosuppression Group II: anti-IL-2R, anti-CD154, belatacept, sirolimus |
5 days > 260 days |
Cardona et al.9 |
| Adult | Cyno (n=3) | Intraportal | ATG, anti-CD154, MMF (Gal-KO/hCD46 transgenic) | > 100 days | Ayares et al.11 |
| Neonatal | Rhesus (n=6) | Intraportal | anti-IL-2R, anti-CD154, belatacept, sirolimus | > 187 days | Russell et al.14 |
| Neonatal | Rhesus (n=5) | Intraportal | anti-CD154, anti-CD25, belatacept, sirolimus | > 76 days | Cardona et al.12 |
| Adult | Cyno (n=10) | Intraportal | Group I (n=2): ATG, anti-CD20, tacrolimus, sirolimus Group II (n=4): ATG, anti-CD154, MMF, cobra venom factor Group III (n=1): ATG, anti-CD154, MMF, dextran sulfate |
< 5 days > 58 days (partial) 3 days |
Rood et al.13 |
| Adult | Cyno (n=9) | Intraportal | Group III (n=1): ATG, anti-CD154, MMF, dextran sulfate | > 60 days (partial) | Casu et al.15 |
| Embryonic | Cyno (n=3) | Omentum | ATG, anti-IL-2R, anti-CD20, CTLA-4Ig, FTY720, everolimus | > 393 days | Hecht et al.16 |
| Adult | Cyno (n=9) | Intraportal | Group I (n=4): ATG, anti-CD154, MMF, dextran sulfate (wild-type pigs) Group II (n=5): ATG, anti-CD154, MMF, dextran sulfate (GKO/hCD46 transgenic) |
< 46 days > 90 days |
van der Windt et al.17 |
| Neonatal | Rhesus (n=10) | Intraportal | Group I (n=5): anti-CD154, anti-LFA-1, CTLA4-Ig, MMF (wild-type pigs) Group II (n=5): anti-CD154, anti-LFA-1, CTLA4-Ig, MMF (GKO transgenic) |
137 days 249 days |
Thompson et al.18 |
| Neonatal | Rhesus (n=9) | Intraportal | Group I (n=3): anti-IL-2R, anti-CD40, belatacept, sirolimus Group II (n=3): same as Group I with additional pre-tx dosing Group III (n=3): anti-IL-2R, belatacept, sirolimus |
> 89 days > 203 days 71 days |
Thompson et al.19 |
| Neonatal | Rhesus (n=13) | Intraportal | Group I (n=3): anti-IL-2R, belatacept, anti-LFA-1, MMF Group II (n=5): anti-IL-2R, belatacept, anti-LFA-1, MMF, tacrolimus Group III (n=5): anti-IL-2R, belatacept, anti-LFA-1, LFA3-Ig, MMF |
< 5 days 99 days 114 days |
Thompson et al.20 |