Peer-Reviewed Journal Details
Mandatory Fields
Lohan, P;Treacy, O;Morcos, M;Donohoe, E;O'donoghue, Y;Ryan, AE;Elliman, SJ;Ritter, T;Griffin, MD
2018
August
Stem Cells (Dayton, Ohio)
Interspecies Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat
Published
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Optional Fields
CORNEAL ALLOGRAFT SURVIVAL STEM-CELLS MEDIATED IMMUNOSUPPRESSION IMMUNE-RESPONSE INHIBIT TRANSPLANTATION EXPRESSION THERAPY MODEL IMMUNOGENICITY
36
1210
1215
Mesenchymal stem/stromal cells (MSC) are an immunomodulatory cell population which are under preclinical and clinical investigation for a number of inflammatory conditions including transplantation. In this study, a well-established rat corneal transplantation model was used to test the ability of human MSC to prolong corneal allograft rejection-free survival using a pre-transplant intravenous infusion protocol previously shown to be efficacious with allogeneic rat MSC. Surprisingly, pre-transplant administration of human MSC had no effect on corneal allograft survival. In vitro, human MSC failed to produce nitric oxide and upregulate IDO and, as a consequence, could not suppress rat T-cell proliferation. Furthermore, human MSC were not activated by rat pro-inflammatory cytokines. Thus, interspecies incompatibility in cytokine signaling leading to failure of MSC licensing may explain the lack of in vivo efficacy of human MSC in a rat tissue allotransplant model. Interspecies incompatibilities should be taken into consideration when interpreting preclinical data efficacy data in the context of translation to clinical trial.
1066-5099
10.1002/stem.2840
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