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Updated: Jul 18, 2026
Modified Langendorff Perfusion for Extended Perfusion Times of Rodent Cardiac Grafts
Published on: June 14, 2024
Ex vivo perfusion with mitomycin C containing solution prolongs heart graft survival in rats
Daohu Wang1, Christian Kleist, Sandra Ehser
1Institute for Immunology, Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
Abstract:
Mitomycin C (MMC) is an alkylating agent which suppresses allogeneic T-cell responses. We analyzed the effect of graft perfusion with MMC on transplant survival. Hearts from Brown-Norway (BN) rats were perfused ex vivo with MMC-containing solution, stored and implanted into Lewis (LEW) rats. In order to analyze the in vivo effect of MMC, recipients received MMC posttransplantation or were pretreated with MMC-incubated donor-derived peripheral blood mononuclear cells (PBMCs). The results show that MMC-perfusion significantly prolongs graft survival. Treatment of recipients with MMC has no effect, whereas MMC-treated donor PBMCs injected into the recipient prolong graft survival. Our findings indicate that the targeted perfusion of donor hearts with MMC-containing solution protects the graft from rejection.
Insights
Perfusion of donor hearts with Mitomycin C (MMC) significantly improves transplant survival in rats. This targeted approach, unlike systemic administration, protects grafts from rejection by suppressing T-cell responses.
Area of Science:
- Immunology
- Transplantation Biology
- Pharmacology
Background:
- Allogeneic T-cell responses are a major barrier to successful organ transplantation.
- Mitomycin C (MMC) is an alkylating agent known to suppress T-cell activity.
Purpose of the Study:
- To investigate the efficacy of ex vivo graft perfusion with Mitomycin C (MMC) on prolonging allogeneic heart transplant survival.
- To compare the effects of targeted graft perfusion versus systemic or cell-based MMC administration on transplant outcomes.
Main Methods:
- Donor rat hearts (Brown-Norway) were perfused ex vivo with an MMC-containing solution before transplantation into recipient rats (Lewis).
- Control groups included recipients treated systemically with MMC post-transplant or pre-treated with MMC-incubated donor PBMCs.
Main Results:
- Ex vivo perfusion of donor hearts with MMC significantly prolonged graft survival compared to controls.
- Systemic administration of MMC to recipients did not improve transplant survival.
- Injection of MMC-treated donor PBMCs into recipients demonstrated a positive effect on graft survival.
Conclusions:
- Targeted perfusion of donor hearts with Mitomycin C is an effective strategy to protect allografts from rejection.
- This localized approach offers a promising method for enhancing transplant success by mitigating immune responses without systemic toxicity.
