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Translational Adipose-derived Stem Cell-Based Immunomodulatory Therapy in a Porcine Hind-limb Transplant Model
Deokyeol Kim1, Francesco Egro1, Alex James Repko1, Matthias Waldner1, Wensheng Zhang1, Joanna Etra2, Damon Cooney2, Mario Solari1, Kacey Marra1, Gerald Brandacher2,* and J. Peter Rubin1,*
1Department of Plastic Surgery, University of Pittsburgh,
2Department of Plastic Surgery, Johns Hopkins University; *Co-Principal Investigator
University of Pittsburgh
2018-02-01
Presenter: Deokyeol Kim
Affidavit:
This is an original study
Director Name: J. Peter Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background: Immunomodulatory effects of mesenchymal stem cells have been confirmed in experimental and clinical studies. The significance of adipose-derived stem cells (ASCs) or bone marrow-derived stem cells (BMSCs) as an immunomodulatory or tolerogenic cell therapy in Vascularized composite allotransplantation (VCA) is just emerging. This study was designed to investigate whether ASC treatment could prolong graft survival in a porcine large animal VCA model.
Methods: Full-/partial- major histocompatibility complex (MHC) mismatched heterotopic hind-limb transplantations were performed in MGH mini-swine. Animals receiving no therapy and animals treated with tacrolimus for 30 days served as control and standard therapy group, respectively. Experimental group animals were treated with tacrolimus for 30 days, followed by ASC or BMSC therapy on postoperative day 7. Allograft survival and mixed lymphocyte reaction were accessed.
Results: A total of eleven hind-limb transplantations were conducted. The control group reached Banff grade 4 acute rejection by day 8. In a partial-MHC mismatch, the mean allograft survival day of BMSC therapy group was 96.5, which was not significantly different from the standard therapy group. The ASC therapy group across a full-MHC mismatch demonstrated grade 4 rejection on day 119 and rejection-free survival over 200 days postoperatively. Both ASC therapy group showed donor-specific unresponsiveness and no histological signs of rejection on day 50 and 100.
Conclusion: On-going experimentation showed promising outcomes of the ASC therapy in prolonging rejection-free VCA survival across full- and partial- MHC mismatch. The ASC therapy promotes donor-specific unresponsiveness in an early stage, which is correlated with immune tolerance.
