Xeno-immunosuppressive properties of human decidual stromal cells in mouse models of alloreactivity in vitro and in vivo

Abstract Background aims Human decidual stromal cells ( h DSCs) may cure acute graft-versus-host disease (GVHD) in humans. We evaluated immunosuppression by xenogenic h DSCs in mice, both in vitro and in vivo . Methods h DSCs inhibited mouse lymphocyte proliferation in allo- and xeno-stimulation assays in mixed lymphocyte culture (MLC) and after mitogenic stimulation. The immunosuppressive effect of h DSCs was dose-dependent and strain-independent. Trans-well experiments showed that h DSCs needed cell-to-cell contact to be immunosuppressive. In a GVHD model, Balb/c mice were transplanted with bone marrow and splenocytes from C57BL/6 a donor. Varying doses of h DSCs (10 5 –10 6 per mouse) were infused at different time points. Recipient mice showed lower GVHD scores than untreated mice, but they did not have consistently improved survival. Histopathological investigation of liver, gastrointestinal tract and skin of animals with GVHD did not show any significant improvement from h DSC infusion. Results h DSCs were transduced with immunosuppressive genes including those encoding interleukin-10, prostaglandin-E2 receptor, indoleamine dioxygenase, interferon-γ and programmed death ligand-1. Transduced and untransduced h DSCs showed similar effects in vitro and in vivo . At a dose of 10 6 h DSCs per mouse, the majority of recipients died of embolism. Conclusions h DSCs inhibit allo-reactivity, xeno-reactivity and mitogen-induced stimulation in mouse lymphocytes. Although the GVHD score was reduced by h DSC infusion, survival and GVHD histopathology were not improved. One reason for failure was fatal embolism.