期刊
TISSUE ENGINEERING PART A
卷 16, 期 3, 页码 1009-1019出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2009.0100
关键词
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资金
- National Institutes of Health [R01 AR50208]
- Hematopoietic Stem Cell Core Facility
- Gene Expression and Genotyping Facility of the Case Comprehensive Cancer Center [P30 CA43703]
We compared human mesenchymal stem cells (hMSCs), expanded long term with and without fibroblast growth factor (FGF) supplementation, with respect to proliferation, and the ability to undergo chondrogenesis in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than the control cells. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at all passages tested although, in some preparations, differentiation was diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage after first passage but exhibited only marginal differentiation after fourth and failed to form cartilage after seventh passage. Microarray analysis of gene expression identified 334 transcripts differentially expressed in fourth passage control cells that had reduced chondrogenic potential, compared with the fourth passage FGF-treated cells that retained this capacity, and 243 transcripts that were differentially expressed when comparing them to the first passage control cells that were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared with the cells that did not. Among these, angiopoietin 1, secreted frizzled-related protein 1, and six transmembrane epithelial antigen of the prostate 1 appear to be of higher relevance. These preliminary data must now be validated to verify whether different gene expression profiles translate into functional differences. In summary, these findings suggest that the chondrogenic potential of hMSCs is vulnerable to cell expansion and that care should be exercised when expanding these cells for cartilage tissue engineering applications. Supplementation with FGF-2 allows reaching target cell numbers more rapidly and extends the level of expansion within which these cells are useful for tissue-engineered cartilage repair.
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