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Differentiation and enrichment of expandable chondrogenic cells from human embryonic stem cells in vitro.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2009 Sep; Vol. 13 (9B), pp. 3570-90. Date of Electronic Publication: 2009 May 01. - Publication Year :
- 2009
-
Abstract
- Human embryonic stem cells (hESCs) are considered as useful tools for pre-clinical studies in regenerative medicine. Although previous reports have shown direct chondrogenic differentiation of mouse and hESCs, low yield and cellular heterogenicity of the resulting cell population impairs the generation of sufficient numbers of differentiated cells for further testing and applications. Based on our previously established high-density micromass model system to study hESC chondrogenesis, we evaluated the effects of transforming growth factor (TGF)-beta(1) and bone morphogenetic protein-2 on early stages of chondrogenic differentiation and commitment by hESCs. Significant chondrogenic induction of hESCs, as determined by quantitative measurements of cartilage-related gene expression and matrix protein synthesis, was achieved in the presence of TGF-beta(1). By means of selective growth factor combination (TGF-beta(1), FGF-2 and platelet-derived growth factor-bb) and plating on extracellular matrix substratum, we report here the reproducible isolation of a highly expandable, homogenous and unipotent chondrogenic cell population, TC1, from chondrogenically committed hESCs. Like primary chondrocytes, TC1 rapidly dedifferentiates upon isolation and monolayer expansion but retains the chondrogenic differentiation potential and responds to TGF-beta(1) for cartilaginous tissue formation both in vitro and in vivo. In addition, TC1 displays a somatic cell cycle kinetics, a normal karyotype and does not produce teratoma in vivo. Thus, TC1 may provide a potential source of chondrogenic cells for drug testing, gene therapy and cell-based therapy.
- Subjects :
- Animals
Cartilage cytology
Cartilage, Articular cytology
Cell Differentiation
Culture Media, Serum-Free metabolism
DNA Primers genetics
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Kinetics
Mice
Transforming Growth Factor beta1 metabolism
Bone Morphogenetic Protein 2 metabolism
Cell Culture Techniques
Chondrocytes cytology
Embryonic Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 13
- Issue :
- 9B
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 19426158
- Full Text :
- https://doi.org/10.1111/j.1582-4934.2009.00762.x