Bone Abstracts

Tissue healing/reconstruction as well as exacerbated inflammatory diseases may benefit from stem cell based therapies. Ex vivo isolated tissue mesenchymal stromal cells (MSCs) displaying multi-potent activity and immune-regulatory functions were long ago proposed as therapeutic cells and already tested in many clinical assays. Nevertheless, their use may be restricted because of the few number that can be recovered from adult tissues, their limited in vitro expansion, and the absence of a full characterization. Other sources of well-defined and unlimited number of MSCs are needed, and MSCs derived in vitro from human Induced Pluripotent Stem (huIPS) cells would be a valuable tool for therapeutic approaches.

We developed a simple assay to generate huiPS–MSCs which were evaluated for their multi-potency and their immunosuppressive activity in vitro and in vivo in a humanized mouse model.

    i) The huiPS–MSCs were phenotypically indistinguishable from tissue MSCs; they were capable of differentiation into osteoblasts, chondrocytes and adipocytes. Co-cultured with stimulated human T lymphocytes, huiPS–MSCs inhibited efficiently the T cell proliferation, switching the T cell cytokine polarization to a regulatory state.

    ii) The in vivo immunosuppressive activity of huiPS-MSCs was evaluated using immune-deficient NOD/SCID/IL2rγKO mice in which human immune cells proliferate, infiltrating tissues. After treatment with huiPS-MSCs, the numbers of human circulating T lymphocytes, of those present in the peritoneal cavity and in the spleen were significantly reduced. Intra-cytoplasmic labelling of recovered T cells showed that untreated mice displayed high percentages of T cells producing inflammatory IFN and TNF cytokines. In contrast, in mice treated with the huiPS-MSCs, the proportion of inflammatory T cells was reduced, while that of T cells producing the anti-inflammatory IL-10 cytokine and expressing the FoxP3 was significantly increased.

We show that in vitro generated multi-potent immune-modulatory huiPS–MSCs may served as new therapeutic tolerogenic tools for inflammatory diseases or for reconstruction/healing processes.