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Impact of Immunosuppressants on Human Adipose-Derived Stem Cells and Bone Marrow-Derived Stem Cells for Cytotherapy
Waldner M, Zhang W, Bliley J, James IB, Havis E, Schweizer R, Plock JA, Marra K, Solari M, Gorantla VS, Rubin JP
University of Pittsburgh, Department of Plastic Surgery
2016-01-31
Presenter: Waldner Matthias
Affidavit:
Hereby I confirm, that all the experiments and specimen collection of the presented work has been performed by the presenting author.
Director Name: J. Peter Rubin
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background: Mesenchymal stem cells derived from bone marrow (BMSC) and adipose tissues (ASC) have clinically useful immunomodulatory effects and low immunogenicity. We assessed and compared the immunomodulatory capacity of BMSCs and ASCs and their susceptibility to immunosuppressive drugs. Herein we compare paired ASCs and BMSCs isolated from the same human donors.
Material and Methods: Omental and s.c. fat tissues and bone marrow aspirates from 9 human organ donors were retrieved and MSCs isolated. The effect of IDs (tacrolimus and sirolimus) on survival and immunomodulative capacity of the MSCs were examined. In mixed lymphocyte reactions (MLR), the ability of ASCs and BMSCs to suppress immune response was assessed and compared within individual donors. Various HLA mismatched stimulation settings were analyzed in co-culture with different MSC concentrations.
Results: The immunomodulating effects of all cell types were dose dependent and altered by the presence of immunosuppressive drugs. Proliferation of responder cells was suppressed by ASCs and BMSCs and combination of both cell types resulted in a highly sufficient immunomodulation. Immunomodulation was not cell contact dependent. ASCs provided an inhibition of stimulated PBMCs of more than 80% (Graph1).
Conclusion: Human ASCs and BMSCs both showed effective immunomodulation across different HLA barriers. The combination of both cell types is an exciting possibility to modulate the immune response. Immunosuppressants affect the immunomodulating function of MSCs via unknown mechanisms.
