Introduction
Rationale for Pig Islet XenoTx
Pig Islet Source, Isolation, and Preparation
Fetal Islets
Neonatal Islets
Adult Islets
Isolation and Preparation
Induction of Diabetes in NHPs
Porcine Islets XenoTx Survival in NHPs
Donor pig age | Recipient | Site of transplantation | Immunosuppression, encapsulation, and/or genetic engineering | Maximum graft survival | Reference |
---|---|---|---|---|---|
Adult | Cyno (n = 8) | Intraportal | None (n = 7) Pretreatment with sCR1 (n = 1) | Post-transplant follow-up for 60 min only | Bennet et al. [23] |
Adult | Baboon (n = 2) | Intraportal | Whole-body and thymic irradiation + ATG + EIA + MMF + CsA + CVF + steroids + αCD154 | >14 d and <28 d | Buhler et al. [39] |
Adult | Baboon (n = 4) | Intraportal | ATG + CsA or LF−195 + MMF + steroids | 2 d | Cantarovich et al. [40] |
Cyno (n = 1) | |||||
Adult | Group 1 | Renal subcapsular and intraportal | Group 1: (cyno) CP + CsA + steroids (rhesus) ATG + α−IL−2R + CsA; steroids | Group 1: 11 d | Rijkelijkhuizen et al. [41] |
Cyno (n = 4) | |||||
Rhesus (n = 4) | |||||
Group 2 | Group 2: ATG + α−IL−2R + CsA; steroids | Group 2: 53 d | |||
Rhesus (n = 4) | |||||
Adult | Rhesus (n = 2) | Intraportal | None | > 3 d | Kirchhof et al. [42] |
Adult | Cyno (n = 15) | Renal subcapsular | Group 1 (n = 12): encapsulation | Group 1: < 180 d | Dufrane et al. [43] |
Group 2 (n = 2): no encapsulation | Groups 2 & 3: < 7 d | ||||
Group 3 (n = 1): empty capsule | |||||
Fetal | Cyno (n = 5) | Renal subcapsular | Group 1: no immunosuppression | Group 1: < 7 d | Mandel [19] |
Group 2: CsA + steroids + CP or BQR | Group 2: > 40 d |
Donor pig age | Recipient | Site of transplantation | Immunosuppression, encapsulation, and/or genetic engineering | Maximum graft survival | Reference |
---|---|---|---|---|---|
Adult | Baboon (n = 3) | Intraportal | ATG + CsA + Aza | < 2 d | Buhler et al. [39] |
Adult | Rhesus (n = 6) | Intraportal | None | > 3 d | Kirchhof et al. [42] |
Adult | Cyno (n = 7) | Renal subcapsular | Group 1 (n = 3): wild-type | Group 1: 3 d | Komoda et al. [44] |
Group 2 (n = 4): GnT-III transgenic islets | Group 2: 5 d | ||||
Adult | Cyno (n = 12) | Intraportal | Group 1 (n = 3): anti-IL-2R + FTY720 + everolimus-anti-CD154 | Group 1: 45 d | Hering et al. [17] |
Group 2 (n = 4): anti-IL-2R + anti-CD154 + FTY720 + everolimus | Group 2: > 187 d | ||||
Group 3 (n = 5): anti-IL-2R + anti-CD154 + FTY720 + everolimus + leflunomide | Group 3: > 158 d | ||||
Adult | Rhesus (n = 5) | Intraportal | Anti-CD25 + anti-CD154 + SRL + belatacept | > 76 d | Cardona et al. [45] |
Adult | Cyno (n = 10) | Intraportal | Group 1 (n = 2): ATG + Tac + SRL + anti-CD20 | Group 1: < 5 d | Rood et al. [13] |
Group 2 (n = 4): ATG + MMF + CVF + anti-CD154 | Group 2: Partial function > 58 d | ||||
Group 3 (n = 1): ATG + MMF + DS + anti-CD154 | Group 3: 3 d | ||||
Adult | Cyno (n = 9) | Intraportal | Group 1 (n = 4) wild-type islets | Group 1: < 46 d | van der Windt et al. [15•] |
Group 2 (n = 5) hCD46 transgenic islets | |||||
Same regimen: ATG + MMF + DS + anti-CD154 | Group 2: > 90 d | ||||
Adult | Cyno (n = 4) | Subcutaneous with islet monolayer device | Encapsulation | 180 d | Gianello and Dufrane [47] |
Neonatal | Rhesus (n = 9) | Intraportal | Group 1 (n = 2): no immunosuppression | Group 1: 5 d | Cardona et al. [16] |
Group 2 (n = 7): ): α-IL-2R + anti-CD154 + SRL + belatacept | Group 2: > 260 d | ||||
Embryonic | Cyno (n = 3) | Omentum | ATG + anti-CD20 + anti-IL-2R + CTLA4-Ig + FTY720 + everolimus | > 393 d | Hecht et al. [48] |