Barberi T, Willis LM, Socci ND, Studer LDerivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med 2:e161

Memorial Sloan-Kettering Cancer Center, New York, New York, United States
PLoS Medicine (Impact Factor: 14.43). 07/2005; 2(6):e161. DOI: 10.1371/journal.pmed.0020161
Source: PubMed


Human embryonic stem cells provide access to the earliest stages of human development and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-restricted precursors.
Here, we present culture conditions for the derivation of unlimited numbers of pure mesenchymal precursors from human embryonic stem cells and demonstrate multilineage differentiation into fat, cartilage, bone, and skeletal muscle cells.
Our findings will help to elucidate the mechanism of mesoderm specification during embryonic stem cell differentiation and provide a platform to efficiently generate specialized human mesenchymal cell types for future clinical applications.

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Available from: Tiziano Barberi, Mar 20, 2015
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    • "Barbet et al. identified differentially expressed genes utilising a Taqman low-density array and reported that hESC-MSC clustered more closely with BM-hMSC than with undifferentiated hESC (Barbet et al., 2011). Barberi et al. utilised affymetrix oligonucleotide arrays on a CD73 + sorted population derived from hESC and compared these with BM-hMSC (Barberi et al., 2005). Similar to our data the authors found enrichment for genes associated with vascular development and inflammatory response/wound healing. "
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    ABSTRACT: Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide an unlimited source of clinical grade cells for therapy. We have generated MSC-like cells from hESC (called here hESC-stromal) that exhibit surface markers and differentiate to osteoblasts and adipocytes, similar to BM-hMSC. In the present study, we used microarray analysis to compare the molecular phenotype of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT). Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undiffer-entiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited ≥2-fold change (FC) in hESC-stromal and BM-hMSC, respectively with 172 genes common to both cell types. Functional annotation of significantly changing genes revealed similarities in gene ontology between the two cell types. Interestingly, genes in categories of cell adhesion/motility and epithelial–mesenchymal transition (EMT) were highly enriched in hESC-stromal whereas genes associated with cell cycle processes were enriched in hMSC-TERT. This data suggests that while hESC-stromal cells exhibit a similar molecular phenotype to hMSC-TERT, differences exist that can be explained by ontological differences between these two cell types. hESC-stromal cells can thus be considered as a possible alternative candidate cells for hMSC, to be employed in regen-erative medicine protocols.
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    • "Several groups described strategies to derive MSC-like cells from either ESCs (Barberi et al., 2005; Boyd et al., 2009) or iPSCs (Liu et al., 2012; Diederichs and Tuan, 2014; Zhang et al., 2011). These approaches were based on coculture with primary MSCs, growth factor combinations , or spontaneous differentiation in embryoid bodies (EBs). "
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    ABSTRACT: Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate toward a ground state and may therefore give rise to more standardized cell preparations. We reprogrammed MSCs into iPSCs, which were subsequently redifferentiated toward MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. However, iPS-MSCs were impaired in suppressing T cell proliferation. DNA methylation (DNAm) profiles of iPSCs maintained donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion, but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs are similar to MSCs, but they reveal incomplete reacquisition of immunomodulatory function and MSC-specific DNAm patterns-particularly of DNAm patterns associated with tissue type and aging.
    Stem Cell Reports 09/2014; 3(3). DOI:10.1016/j.stemcr.2014.07.003 · 5.37 Impact Factor
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    • "Please cite this article in press as : Wang et al . , Human ESC - Derived MSCs Outperform Bone Marrow MSCs in the Treatment of an EAE Model of Multiple Sclerosis , Stem Cell Reports ( 2014 ) , http : / / dx . doi . org / 10 . 1016 / j . stemcr . 2014 . 04 . 020 sorting , scraping , or handpicking of cells ( Barberi et al . , 2005 ; Brown et al . , 2009 ; Gruenloh et al . , 2011 ; Hwang et al . , 2008 ; Olivier et al . , 2006 ; Vodyanik et al . , 2010 ) , which limits the efficiency and purity of the hES - MSCs , as well as the ability to scale up their production . hES - MSCs have been used in some disease models , such as inflammatory bowel disease , lupus , an"
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    ABSTRACT: Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs) may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE) model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs). Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE.
    Stem Cell Reports 07/2014; 3(1):1-16. DOI:10.1016/j.stemcr.2014.04.020 · 5.37 Impact Factor
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