Prolonged survival of discordant porcine islet xenografts

Abstract: Purified porcine islets were prepared by collagenase digestion and density gradient purification, and transplanted under the kidney capsule of C57B/B6 mice with streptozotocin-induced diabetes which were receiving varying temporary immunosuppressive therapies. Islets that had been cultured for 1 day at 37 degrees C were rejected after: 9 +/- 0.1 (mean +/- SE) days in control mice; 14 +/- 3 days in mice receiving mouse antilymphocyte serum (MLS) plus porcine antilymphocyte serum (PLS) on day of transplant (day 0); 43 +/- 8 days in mice treated for 1 week with anti-CD4 antibody (aCD4); 36 +/- 4 days in mice given aCD4 for 1 week plus PLS on days 0 and 7; 47 +/- 3 days in mice treated with aCD4 for 1 week plus MLS and PLS on day 21. Porcine islet survival in these latter three groups was significantly (P<0.01) and similarly longer than in the control and MLS plus PLS groups. Then, we transplanted islets that had been either cultured at 24 degrees C for 7 days or cryopreserved into 7-day aCD4-treated mice, to evaluate whether low temperature culture or the freezing-thawing procedure could affect survival. Neither 7-day, low temperature culture (mean survival time: 37 +/- 2 days) nor cryopreservation (mean survival time: 39 +/- 2 days) prolonged islet function further. Thus, the present study demonstrates that prolonged survival can be achieved with discordant porcine islet xenografts, and shows the greater efficacy of aCD4 treatment, which was not improved by the additional immunosuppressive therapies we tested, nor by culture or cryopreservation of the islets.