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The derivation of mesenchymal progenitors from human embryonic stem cells (hESCs) has recently been reported. We studied the immune characteristics of these hESC‐derived mesenchymal progenitors (EMPs) and their interactions with T lymphocytes and natural killer cells (NKs), two populations of lymphocytes with important roles in transplantation immunology. EMPs express a number of bone marrow mesenchymal stromal cell (BMMSC) markers, as well as the hESC marker SSEA‐4. Immunologically, EMPs do not express HLA‐DR or costimulatory molecules. On the other hand, HLA‐G, a nonclassic MHC I protein involved in mediating maternal‐fetal tolerance, can be found on the surface of EMPs, and its expression is increased after interferon‐γ stimulation. EMPs can suppress CD4 +  or CD8 +  lymphocyte proliferation, similar to BMMSCs. However, EMPs are more resistant to NK‐mediated lysis than BMMSCs and can suppress the cytotoxic effects of activated NKs, as well as downregulating the NK‐activating receptors NKp30 and NKp46. With their broad immunosuppressive properties, EMPs may represent a new potential cell source for therapeutic use. S TEM  C ELLS   2009;27:451–456

stem cells

Brief Report—Human Embryonic Stem Cell‐Derived Mesenchymal Progenitors Possess Strong Immunosuppressive Effects Toward Natural Killer Cells as Well as T Lymphocytes