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
Stem Cells
Interspecies Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat
Optional Fields
Corneal transplant; Cytokines; Immunomodulation; Mesenchymal stem/stromal cell; Transplantation; Xenogeneic
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.
Grant Details
EU, Science Foundation Ireland (SFI)
Publication Themes
Biomedical Science and Engineering