title: Molecular characterisation of stromal populations derived from human embryonic stem cells: Similarities to immortalised bone marrow derived stromal stem cells.
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 undifferentiated 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 regenerative medicine protocols.
authors.affiliation: Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: Linda
authors.initials: L
authors.lastname: Harkness
authors.affiliation: Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark; NSW Systems Biology Initiative, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Twine
authors.affiliation: Molecular Embryology and Aging group, Max-Planck Institute for Molecular Genetics (Department of Vertebrate Genomics), Berlin, Germany; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Raed
authors.initials: R
authors.lastname: Abu Dawud
authors.affiliation: Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Danish Stem Cell Centre (DanStem), Institute of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Abbas
authors.initials: A
authors.lastname: Jafari
authors.affiliation: Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Aldahmash
authors.affiliation: NSW Systems Biology Initiative, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Wilkins
authors.affiliation: Molecular Embryology and Aging group, Max-Planck Institute for Molecular Genetics (Department of Vertebrate Genomics), Berlin, Germany; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Institute for Stem Cell Research and Regenerative Medicine, Faculty of Medicine, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
authors.affiliation: Molecular Endocrinology Laboratory, Odense University Hospital, University of Southern Denmark, Odense, Denmark; Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Danish Stem Cell Centre (DanStem), Institute of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
keywords: Bioinformatic analysis; Bone marrow stromal cells; Illumina bead microarray; Osteoblastic differentiation; Pluripotent stem cells