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PMID: 19196144 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Human embryonic stem cell-derived mesoderm-like epithelium transitions to mesenchymal progenitor cells.

Tissue engineering. Part A ·Vol. 15 ·No. 8 ·2009-08-00 ·Pages 1897-907

Boyd NL, Robbins KR, Dhara SK, West FD, Stice SL

Abstract

Human embryonic stem cells (hESC) have the potential to produce all of the cells in the body. They are able to self-renew indefinitely, potentially making them a source for large-scale production of therapeutic cell lines. Here, we developed a monolayer differentiation culture that induces hESC (WA09 and BG01) to form epithelial sheets with mesodermal gene expression patterns (BMP4, RUNX1, and GATA4). These E-cadherin+ CD90low cells then undergo apparent epithelial-mesenchymal transition for the derivation of mesenchymal progenitor cells (hESC-derived mesenchymal cells [hES-MC]) that by flow cytometry are negative for hematopoietic (CD34, CD45, and CD133) and endothelial (CD31 and CD146) markers, but positive for markers associated with mesenchymal stem cells (CD73, CD90, CD105, and CD166). To determine their functionality, we tested their capacity to produce the three lineages associated with mesenchymal stem cells and found they could form osteogenic and chondrogenic, but not adipogenic lineages. The derived hES-MC were able to remodel and contract collagen I lattice constructs to an equivalent degree as keloid fibroblasts and were induced to express alpha-smooth muscle actin when exposed to transforming growth factor (TGF)-beta1, but not platelet derived growth factor-B (PDGF-B). These data suggest that the derived hES-MC are multipotent cells with potential uses in tissue engineering and regenerative medicine and for providing a highly reproducible cell source for adult-like progenitor cells.

MeSH Terms
Actins/metabolism Adipogenesis/drug effects Animals Becaplermin Biomarkers/metabolism Cell Line Chondrogenesis/drug effects Collagen Type I/metabolism Embryonic Stem Cells/cytology,drug effects,metabolism Epithelial Cells/cytology,drug effects Flow Cytometry Humans Mesenchymal Stem Cells/cytology,drug effects Mesoderm/cytology,drug effects Mice Osteogenesis/drug effects Phenotype Platelet-Derived Growth Factor/pharmacology Proto-Oncogene Proteins c-sis Rats Transforming Growth Factor beta1/pharmacology
Chemicals
Actins Biomarkers Collagen Type I Platelet-Derived Growth Factor Proto-Oncogene Proteins c-sis Transforming Growth Factor beta1 Becaplermin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Boyd Nolan L
Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
Robbins Kelly R
Dhara Sujoy K
West Franklin D
Stice Steven L
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Article Info
Journal
Tissue engineering. Part A
Abbr.
Tissue Eng Part A
ISSN
1937-335X
DOI
10.1089/ten.tea.2008.0351
Published
2009-08-00
Pages
1897-907
Language
English
Region
United States
NLM ID
101466659
PMCID
PMC2792108
Subset
IM
External Links
PubMed source DOI: 10.1089/ten.tea.2008.0351 PMC Full Text View journal details
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