Efficient Derivation and Concise Gene Expression Profiling of Human Embryonic Stem Cell-Derived Mesenchymal Progenitors (EMPs)

Department of Primary Care Medicine & Department of Obstetrics/Gynecology, National Taiwan University Hospital & College of Medicine, National Taiwan University, Taipei, Taiwan
Cell Transplantation (Impact Factor: 3.13). 09/2011; 20(10):1529-1545. DOI: 10.3727/096368910X564067


New potential sources of stem cells for clinical application include bone marrow mesenchymal stem cells (BMMSCs), human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPS). However, each source is not without its own concerns. While research continues in an effort to overcome these problems, the generation of mesenchymal progenitors from existing hESC lines may circumvent many of these issues. We report here a simple and efficient method of generating hESC-derived mesenchymal progenitors (EMPs) and transcriptome profiling using a concise, custom-designed, oligomnucleotide gene expression microarray. Characterization of EMPs shows that these cells are similar to BMMSCs in terms of differentiation capacity as well as cell surface marker expression. In addition, EMPs express several ESC markers and HLA-G, a nonclassical MHC class I molecule with immunomodulatory properties. Morevoer, EMPs possess significantly enhanced proliferative ability over BMMSCs during which karyotypic stability was maintained. Although derived from hESCs, EMPs do not form any tumors in immunocompromised mice. To efficiently profile gene expression in multiple samples, we designed an oligoarray to probe just over 11,000 genes highly expressed in stem cells. We found that the transcriptome of EMPs is more similar to BMMSCs than hESCs. Both cell types highly express genes involved in processes related to the cytoskeleton, extracellular matrix, and cell adhesion, but EMPs show higher expression of genes involved in cell proliferation whereas BMMSCs showed higher expression of immune-related genes. Based on our data, EMPs may be an accessible source of mesenchymal progenitor for therapeutic use.

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    • "For instance, HLA-G and HLA-E are non-classical MHC class Ib molecules that are essential in the acceptance of an embryo. To investigate whether PSCs also take advantage of these molecules, a study conducted by Yen et al. revealed that hESC-derived mesenchymal progenitor cells (MPCs) were resistant to NK cell lysis, coinciding with high HLA-G expression on the surface [37]. Furthermore, several reports claimed that this resistance to NK cell cytotoxicity exists, by showing contradicting results in NKG2D ligand expression. "
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    Current Stem Cell Research & Therapy 10/2013; 9(1). DOI:10.2174/1574888X113086660068 · 2.21 Impact Factor
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    • "Most MSCs derivations are achieved via the formation of three-dimensional embryoid bodies, which are laborious, inefficient and uncontrollable for spontaneous differentiation14. Yen et al. have described a simple method of differentiating human ES cells (hESCs) into MSCs by switching hES cells from ES medium to defined medium, which consisted of DMEM-low glucose, 10% FBS, and 1% Penicillin/Streptomycin, followed by trypsinization-based passaging15. In this study, we investigated whether this method can be applied to human iPS cells. "
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