Tierarztl Prax Ausg K Kleintiere Heimtiere 2019; 47(02): 140-141
DOI: 10.1055/s-0039-1679124
Poster
Georg Thieme Verlag KG Stuttgart · New York

The effects of mitomycin C-treated peripheral blood mononuclear cells combined with cyclosporine A in vascularized composite allotransplantation in the rat hind limb model

C Fejös
1   Institute for Veterinary Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Justus-Liebig University, Gießen, Germany
,
J Kiefer
2   BG-Trauma Centre, Department of Hand and Plastic Surgery, University of Heidelberg, Germany
,
C Radu
2   BG-Trauma Centre, Department of Hand and Plastic Surgery, University of Heidelberg, Germany
,
U Kneser
2   BG-Trauma Centre, Department of Hand and Plastic Surgery, University of Heidelberg, Germany
,
S Wenisch
1   Institute for Veterinary Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Justus-Liebig University, Gießen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
23 April 2019 (online)

 

Introduction:

Vascularized composite allotransplantation (VCA) refers to the transfer of functional units, which consist of immunologically different tissue types. While it represents a potential treatment option for patients with complex tissue injuries, lifelong immunosuppressive drug regimen can lead to severe side effects. In previous VCA studies, the immunomodulatory ability of mitomycin C-treated peripheral blood mononuclear cells (MMC-treated PBMCs) has already been shown.

Goal:

The aim of this study was to potentiate the immunosuppressive effect of MMC-treated PBMCs through cyclosporine A (CsA) in the rat hind limb model in order to supress T cell response, avoid acute rejection and prolong graft survival.

Method:

PBMCs were extracted from donor blood and incubated with MMC. Fifty mismatched rat hind limb transplantations were conducted, where Lewis rats were graft donors and Brown Norway rats were recipients. Groups A and B received MMC-treated PBMCs, with group A receiving a full dose and group B receiving a reduced dose of CsA for 7 days postoperatively. Recipients of control groups C and D received solely a full dose and reduced dose of CsA for 7 days, whereas group E did not receive immunosuppression. The grafts were assed clinically every 8 hours until rejection occurred.

Results:

Based on the rejection-free period a significant (p < 0.0001) delay was demonstrated when comparing groups A, B with the corresponding controls C, D and E. A full dose of CsA (C) had a positive effect on graft survival when matched to the group with no immunosuppression (E). However, a clear potentiating effect (p < 0.0001) was shown in groups receiving cell therapy combined with CsA (A, B) compared to the groups with CsA alone (C, D). Conclusion:

These data show that CsA combined with MMC-treated PBMCs has a potentiating immunosuppressive effect and significantly prolongs allograft survival in the VCA model.