Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Abstract

Objective-We have previously shown the simultaneous generation of CD73+ mesenchymal stromal cells (MSCs) along with CD34+ hematopoietic cells from human embryonic stem cells (ESCs) when they are co-cultured with OP9 murine stromal cells. We investigated whether MSCs can be derived from human ESCs without co-culturing with OP9 cells, and if such cells exhibit immunological properties similar to MSCs derived from adult human bone marrow (BM).Materials and Methods-Our starting populations were undifferentiated ESCs cultured on matrigel-coated plates without feeder cells. The differentiated fibroblast-looking cells were tested for expression of MSC markers and their potential for multi-lineage differentiation. We investigated surface expression of HLA molecules on these MSCs before and after treatment with interferon gamma (IFN-γ). We also tested the proliferative response of T-lymphocytes towards MSCs and the effects of MSCs in mixed lymphocyte reaction (MLR) assays. Conclusions-MSCs can be derived from human ESCs without feeder cells. These human ESCderived MSCs have cell surface markers, differentiation potentials, and immunological properties in vitro that are similar to adult BM-derived MSCs. Results-We

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

“…In previous studies, different protocols have been described to derive MSC-like cells from hESCs, including co-culture with mouse OP9 cells (Barberi et al, 2005), embryoid body differentiation (Hwang et al, 2008), spontaneous differentiation in monolayer (Trivedi and Hematti, 2008), selection of cell populations by FACS (Lian et al, 2007), and mechanical separation (Olivier et al, 2006). Here we developed a novel, simplified method to obtain a morphologically homogeneous hESC-MSC population.…”

“…Likewise, hESC-MSCs have a strong immunosuppressive effect on lymphocytes in vitro. Trivedi and Hematti (2008) and Yen et al (2009) have reported that hESC-MSCs can suppress proliferation of T lymphocytes derived from peripheral blood MNCs. Our findings from MLRs of xenogenic lymphocytes and hESC-MSCs further support their results.…”

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

“…There are only a few small pilot studies of MSC therapy using an alternative source for refractory acute GVHD [54,55]. In the near future, embryonic stem cells [56] and induced pluripotent stem cells [57] could be available for MSC source. The usage of alternative sources is experimental and further studies are needed for practical clinical applications.…”

Embryonic Stem Cell-Derived Multipotent Mesenchymal Stromal Cell Therapy Following Focal Ischemia in the Rat

“…Furthermore, MSCs evade natural killer cell or cytotoxic lymphocyte-mediated cell lysis, despite lysis of other cell types from the same donor (Rasmusson et al 2003). Not only do they avoid stimulating lymphocyte proliferation, MSCs can suppress T cell activation in mixed lymphocyte reaction assays (Aggarwal & Pittenger 2005;Trivedi & Hematti 2008) www.intechopen.com…”