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
May
Stem Cells
Interspecies Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat
Published
()
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.
10.1002/stem.2840
Grant Details
EU, Science Foundation Ireland (SFI)
Publication Themes
Biomedical Science and Engineering