Permanent acceptance of mitomycin C-treated islet allograft.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Matsuyama
Shinichi
S
Department of Surgery I, Fukushima Medical University, Fukushima, Japan.
Gunji
Takashi
T
Ise
Kazuya
K
Sato
Yoshihiro
Y
Saito
Takuro
T
Gotoh
Mitsukazu
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D016685:Mitomycin