Interspecies Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat. (16th May 2018)

• Record Type: Journal Article
• Authors: Lohan, Paul; Treacy, Oliver; Morcos, Maurice; Donohoe, Ellen; O'donoghue, Yvonne; Ryan, Aideen E.; Elliman, Stephen J.; Ritter, Thomas; Griffin, Matthew D.
• Is Part Of: Stem cells. Volume 36:Number 8(2018)
• Page Start: 1210
• Page End: 1215
• Publication Date: 2018-05-16
• Subjects: Mesenchymal stem/stromal cell -- Corneal transplant -- Immunomodulation -- Cytokines -- Xenogeneic -- Transplantation; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2840
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : 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. Abstract : In the context of cornea transplantation, allogeneic rat mesenchymal stem/stromal cells (MSC) can be administered intra-venously to cornea transplant recipients resulting in extended rejection free graft survival times. Additionally rat MSC, when exposed to rat pro-inflammatory cytokines such as Interferon-γ, tumor necrosis factor-α, and interleukin 1β, increase production of the immunomodulatory molecule nitric oxide as well as increasing their immunomodulatory abilities. On the other hand, human MSC, when administered in an identical protocol to rat MSC, are incapable of extending corneal allograft rejection free survival. Also, exposure of human MSC to rat pro-inflammatory cytokines results in no production of nitric oxide or increased T cell immunomodulatory ability.