Data against a Common Assumption: Xenogeneic Mouse Models Can Be Used to Assay Suppression of Immunity by Human MSCs
Authors: Darwin J. Prockop, Joo Youn Oh, Ryang Hwa Lee
Journal: Molecular Therapy (2017)

Much of what we know about immunology suggests that little is to be gained from experiments in which human cells are administered to immunocompetent mice. Multiple reports have demonstrated that this common assumption does not hold for experiments with human mesenchymal stem/stromal cells (hMSCs). The data demonstrate that hMSCs can suppress immune responses to a variety of stimuli in immunocompetent mice by a range of different mechanisms that are similar to those employed by mouse MSCs. Therefore, further experiments with hMSCs in mice will make it possible to generate preclinical data that will improve both the efficacy and safety of the clinical trials with the cells that are now in progress. Much of what we know about immunology suggests that little is to be gained from experiments in which human cells are administered to immunocompetent mice. Multiple reports have demonstrated that this common assumption does not hold for experiments with human mesenchymal stem/stromal cells (hMSCs). The data demonstrate that hMSCs can suppress immune responses to a variety of stimuli in immunocompetent mice by a range of different mechanisms that are similar to those employed by mouse MSCs. Therefore, further experiments with hMSCs in mice will make it possible to generate preclinical data that will improve both the efficacy and safety of the clinical trials with the cells that are now in progress. One of the established tenets of immunity is that cells lacking the "self" markers, such as major histocompatibility complex (MHC) class I molecules, are quickly destroyed by immune responses. Therefore, there seemed to be little to be gained from experiments in which human cells were infused into immunocompetent mice. Surprisingly, an exception to this conclusion has come from experiments with human mesenchymal stem/stromal cells (hMSCs). A large series of reports have demonstrated that hMSCs can effectively suppress immune responses in immunocompetent mice (see Table 1 for examples). The hMSCs can also generate immune responses but less than other cells, and under many conditions, the immunosuppressive effects predominate.1Eliopoulos N. Stagg J. Lejeune L. Pommey S. Galipeau J. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice.Blood. 2005; 106: 4057-4065Crossref PubMed Scopus (343) Google Scholar, 2Ankrum J.A. Ong J.F. Karp J.M. Mesenchymal stem cells: immune evasive, not immune privileged.Nat. Biotechnol. 2014; 32: 252-260Crossref PubMed Scopus (259) Google Scholar The consequences of these observations are not trivial. A major consequence is that the xenogeneic mouse models can be used to assay the efficacy of hMSCs and thereby provide some preclinical data that are essential for well-designed trials in patients.3Muller P.Y. Milton M.N. 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