Immunomodulative effects of mesenchymal stem cells derived from human embryonic stem cells in vivo and in vitro*

Objective: Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs). The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs), but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation model. Methods: Undifferentiated hESCs were treated with Rho-associated kinase (ROCK) inhibitor and induced to fibroblast-looking cells. These cells were tested for their surface markers and multilineage differentiation capability. Further more, we analyzed their immune characteristics by mixed lymphocyte reactions (MLRs) and animal experiments. Results: hESC-MSCs show a homogenous fibroblastic morphology that resembles bone marrow-derived MSCs (BM-MSCs). The cell markers and differentiation potential of hESC-MSCs are also similar to those of BM-MSCs. Unlike their original cells, hESC-MSCs possess poor immunogenicity and can survive and be engrafted into a xenogenic immunocompetent environment. Conclusions: The hESC-MSCs demonstrate strong inhibitory effects on lymphocyte proliferation in vitro and anti-inflammatory infiltration properties in vivo. This study offers information essential to the applications of hESC-MSC-based therapies and evidence for the therapeutic mechanisms of action