The combination of mitomycin-induced blood cells with a temporary treatment of ciclosporin A prolongs allograft survival in vascularized composite allotransplantation

• Verfasst von: Radu, Christian Andreas [VerfasserIn]
• Verfasst von: Fischer, Sebastian [VerfasserIn]
• Verfasst von: Diehm, Yannick [VerfasserIn]
• Verfasst von: Dittmar, Laura [VerfasserIn]
• Verfasst von: Kleist, Christian [VerfasserIn]
• Verfasst von: Gebhard, Martha-Maria [VerfasserIn]
• Verfasst von: Terness, Peter [VerfasserIn]
• Verfasst von: Kneser, Ulrich [VerfasserIn]
• Verfasst von: Kiefer, Jurij [VerfasserIn]
• Titel: The combination of mitomycin-induced blood cells with a temporary treatment of ciclosporin A prolongs allograft survival in vascularized composite allotransplantation
• Verf.angabe: Christian Andreas Radu, Sebastian Fischer, Yannick Diehm, Otto Hetzel, Florian Neubrech, Laura Dittmar, Christian Kleist, Martha Maria Gebhard, Peter Terness, Ulrich Kneser, Jurij Kiefer
• Jahr: 2018
• Umfang: 10 S.
• Fussnoten: Published online: 19 August 2017 ; Gesehen am 23.10.2018
• Titel Quelle: Enthalten in: Langenbeck's archives of surgery
• Ort Quelle: Berlin : Springer, 1948
• Jahr Quelle: 2018
• Band/Heft Quelle: 403(2018), 1, Seite 83-92
• ISSN Quelle: 1435-2451
• DOI: doi:10.1007/s00423-017-1616-3
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cell therapy
• Sach-SW: MICs
• Sach-SW: Mitomycin C
• Sach-SW: Mitomycin-induced cells
• Sach-SW: Peripheral blood mononuclear cells
• Sach-SW: Vascularized composite allotransplantation
• K10plus-PPN: 1582179026

Abstract

Background: Vascularized composite allotransplantation (VCA) is a rapidly expanding field of transplantation and provides a potential treatment for complex tissue defects. Peripheral blood mononuclear cells (PBMCs) shortly incubated with the antibiotic and chemotherapeutic agent mitomycin C (MMC) can suppress allogeneic T cell response and control allograft rejection in various organ transplantation models. MMC-incubated PBMCs (MICs) are currently being tested in a phase I clinical trial in kidney transplant patients. Previous studies with MICs in a complex VCA model showed the immunomodulatory potential of these cells. The aim of this study is to optimize and evaluate the use of MICs in combination with a standard immunosuppressive drug in VCA. Methods: Fully mismatched rats were used as hind limb donors [Lewis (RT11)] and recipients [Brown-Norway (RT1n)]. Sixty allogeneic hind limb transplantations were performed in six groups. Group A received donor-derived MICs combined with a temporary ciclosporin A (CsA) treatment. Group B received MICs in combination with a temporarily administered reduced dose of CsA. Group C served as a control and received a standard CsA dose temporarily without an additional administration of MICs, whereas Group D was solely medicated with a reduced CsA dose. Group E received no immunosuppressive therapy, neither CsA nor MICs. Group F was given a continuous standard immunosuppressive regimen consisting of CsA and prednisolone. The endpoint of the study was the onset of allograft rejection which was assessed clinically and histologically. Results: In group A and B, the rejection-free interval of the allograft was significantly prolonged to an average of 23.1 ± 1.7 and 24.7 ± 1.8 days compared to the corresponding control groups (p < 0.01). Rejection in groups C, D, and E was noted after 14.3 ± 1.1, 7.8 ± 0.7, and 6.9 ± 0.6 days. No rejection occurred in control group F during the follow-up period of 100 days. No adverse events have been noted.Conclusion: The findings of this study show that the combination of MICs with a temporary CsA treatment significantly prolongs the rejection-free interval in a complex VCA model. The combination of MICs with CsA showed no adverse events such as graft-versus-host disease. MICs, which are generated by a simple and reliable in vitro technique, represent a potential therapeutic tool for prolonging allograft survival through immunomodulation.