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Mesenchymal stem cell-based immunomodulatory therapy in a swine hindlimb allotransplantation model
Deokyeol Kim, Matthias Waldner, Angelo Leto Barone, Damon Cooney, Mario Solari, Kacey Marra, Vijay Gorantla, Gerald Brandacher, and Peter Rubin
Department of Plastic Srugery, University of Pittsburgh
2017-02-14
Presenter: Deokyeol Kim
Affidavit:
This is original work.
Director Name: Peter J Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background: Recent studies have shown that mesenchymal stem cells have immunomodulatory effects and low immunogenicity. Bone marrow-derived stem cells (BMSCs) are already being introduced clinically for immunomodulation in vascularized tissue allotransplantaion. Adipose-derived stem cells (ASCs) may constitute another clinically useful source of cell therapy for allotransplantation. This study was designed to investigate whether ASCs treatment could prolong composite tissue allotransplant survival in a large animal model.
Methods: Heterotropic hindlimb transplantations were performed in MGH mini-swine across major and minor histocompatibility complex (HC) mismatch. Conditions included control animals receiving no therapy, animals treated with a standard immunosuppressive drug, standard immunosuppressive protocol with BMSCs therapy, and standard immunosuppressive protocol with ASCs therapy. For cell therapy, donor-derived ASCs/BMSCs were intravenously injected into recipient animals at day 7 postoperatively. The allografts' survival were compared amongst the different treatment protocols.
Results: Allotransplants in the control group without treatment across both major and minor HC mismatch reached Banff grade 4 total rejection by day 8 postoperatively. The mean allograft survival day of BMSCs therapy group in minor HC mismatch was 96.5, which is not significantly different compared to standard immunosuppressive group. ASCs therapy groups in both major and minor HC mismatch are currently being observed.
Conclusion: Early results of ongoing in vivo experimentation showed promising results of cell treatment to modulate immune response across major and minor HC mismatch. More results are needed to fully demonstrate the immunomodulatory effects of ASCs and BMSCs in vascularized composite allotransplantation.
