A VISICORT study was published recently in Stem Cells. The body of research entitled “Inter‐Species Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat” by Paul Lohan, Oliver Treacy, Maurice Morcos, Ellen Donohoe, Yvonne O’Donoghue, Aideen E Ryan, Stephen J Elliman, Thomas Ritter and Matthew D Griffin was accepted for publication on 13 April 2018.
Mesenchymal stem/stromal cells (MSC) are an immunomodulatory cell population which are under pre‐clinical 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 signalling leading to failure of MSC licensing may explain the lack of in vivo efficacy of human MSC in a rat tissue allotransplant model. Inter‐species incompatibilities should be taken into consideration when interpreting pre‐clinical data efficacy data in the context of translation to clinical trial.