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Tissue engineering with chondrogenically differentiated human embryonic stem cells. Stem Cells 2007 Sep;25(9):2183-90

Date

06/02/2007

Pubmed ID

17540854

DOI

10.1634/stemcells.2007-0105

Scopus ID

2-s2.0-34748851909   78 Citations

Abstract

This study describes the development and application of a novel strategy to tissue engineer musculoskeletal cartilages with human embryonic stem cells (hESCs). This work expands the presently limited understanding of how to chondrogenically differentiate hESCs through the use of chondrogenic medium alone (CM) or CM with two growth factor regimens: transforming growth factor (TGF)-beta3 followed by TGF-beta1 plus insulin-like growth factor (IGF)-I or TGF-beta3 followed by bone morphogenic protein (BMP)-2. It also extends the use of the resulting chondrogenically differentiated cells for cartilage tissue engineering through a scaffoldless approach called self-assembly, which was conducted in two modes: with (a) embryoid bodies (EBs) or (b) a suspension of cells enzymatically dissociated from the EBs. Cells from two of the differentiation conditions (CM alone and TGF-beta3 followed by BMP-2) produced fibrocartilage-like constructs with high collagen I content, low collagen II content, relatively high total collagen content (up to 24% by dry weight), low sulfated glycosaminoglycan content (approximately 4% by dry weight), and tensile properties on the order of megapascals. In contrast, hESCs treated with TGF-beta3 followed by TGF-beta1 + IGF-I produced constructs with no collagen I. Results demonstrated significant differences among the differentiation conditions in terms of other biochemical and biomechanical properties of the self-assembled constructs, suggesting that distinct growth factor regimens differentially modulate the potential of the cells to produce cartilage. Furthermore, this work shows that self-assembly of cells obtained by enzymatic dissociation of EBs is superior to self-assembly of EBs. Overall, the results of this study raise the possibility of manipulating the characteristics of hESC-generated tissue toward specific musculoskeletal cartilage applications.

Author List

Koay EJ, Hoben GM, Athanasiou KA

Author

Gwendolyn M B Hoben MD Assistant Professor in the Plastic Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Biomechanical Phenomena
Cell Differentiation
Cells, Cultured
Chondrocytes
Chondrogenesis
Embryonic Stem Cells
Humans
Mice
Tissue Engineering
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