PERMANENT ACCEPTANCE OF MITOMYCIN C-TREATED ISLET ALLOGRAFT
- 1 July 2003
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Transplantation
- Vol. 76 (1), 65-71
- https://doi.org/10.1097/01.tp.0000069232.48055.03
Abstract
Mitomycin C (MMC) treatment produces genotoxic stress and exerts various biologic effects on cell function. This study determines the feasibility of MMC pretreatment of islet grafts as a sole immunomodulatory regimen to protect murine crude-digested islet allografts. Collagenase-digested BALB/c (H-2d) islets were incubated for 30 min with MMC at different doses (0, 3.2, 10, 32, and 100 microg/mL; n=20, 15, 55, 15, 15, respectively), cultured for 20 hr, and transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (B6; H-2b) mice. All mice that received MMC-treated islets showed restoration of normoglycemia within 5 days postgrafting, which was maintained until rejection. All untreated islets were acutely rejected with a mean survival time of 15.1+/-3.5 days. Significant prolongation of graft survival was noted in mice undergoing transplantation with islets treated with 10 microg/mL MMC compared with untreated islets (58.9+/-37.7 days, P<0.01). Notably, the grafts of 24 of 55 animals (43%) that received islets treated with 10 microg/mL MMC survived more than 100 days without any other treatment. Furthermore, antigen-specific prolongation of graft survival of secondary untreated islets was observed in mice bearing long-term functioning islet grafts. Our results indicate that pretreatment of islets with MMC alone protects the graft against rejection and produces long-term graft survival with normal blood glucose levels, and that pretreatment with MMC offers a new strategy for allogeneic islet transplantation.Keywords
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