Comparative analysis of mesenchymal stem cell and embryonic tendon progenitor cell response to embryonic tendon biochemical and mechanical factors

Advances in tendon engineering with mesenchymal stem cells (MSCs) are hindered by a need for cues to direct tenogenesis, and markers to assess tenogenic state. We examined the effects of factors involved in embryonic tendon development on adult MSCs, and compared MSC responses to that of embryonic t...

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Published in:	Stem cell research & therapy 2015-05, Vol.6 (1), p.89-89, Article 89
Main Authors:	Brown, Jeffrey P, Galassi, Thomas V, Stoppato, Matteo, Schiele, Nathan R, Kuo, Catherine K
Format:	Article
Language:	eng
Subjects:	Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Bone Marrow Cells - cytology Cell Proliferation - drug effects Cells, Cultured Collagen Collagen Type I - genetics Collagen Type I - metabolism Comparative analysis Down-Regulation - drug effects Elastin Elastin - genetics Elastin - metabolism Embryonic Stem Cells - cytology Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism Fibroblast Growth Factor 4 - genetics Fibroblast Growth Factor 4 - metabolism Fibroblast Growth Factor 4 - pharmacology Growth factors Health aspects Male Membrane Proteins - genetics Membrane Proteins - metabolism Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - metabolism Methods Mice Mice, Transgenic Recombinant Proteins - biosynthesis Recombinant Proteins - isolation & purification Recombinant Proteins - pharmacology RNA Tendons - cytology Tensile Strength Transcriptome - drug effects Transforming Growth Factor beta2 - genetics Transforming Growth Factor beta2 - metabolism Transforming Growth Factor beta2 - pharmacology
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Summary:	Advances in tendon engineering with mesenchymal stem cells (MSCs) are hindered by a need for cues to direct tenogenesis, and markers to assess tenogenic state. We examined the effects of factors involved in embryonic tendon development on adult MSCs, and compared MSC responses to that of embryonic tendon progenitor cells (TPCs), a model system of tenogenically differentiating cells. Murine MSCs and TPCs subjected to cyclic tensile loading, transforming growth factor-β2 (TGFβ2), and fibroblast growth factor-4 (FGF4) in vitro were assessed for proliferation and mRNA levels of scleraxis, TGFβ2, tenomodulin, collagen type I and elastin. Before treatment, scleraxis and elastin levels in MSCs were lower than in TPCs, while other tendon markers expressed at similar levels in MSCs as TPCs. TGFβ2 alone and combined with loading were tenogenic based on increased scleraxis levels in both MSCs and TPCs. Loading alone had minimal effect. FGF4 downregulated tendon marker levels in MSCs but not in TPCs. Select tendon markers were not consistently upregulated with scleraxis, demonstrating the importance of characterizing a profile of markers. Similar responses as TPCs to specific treatments suggest MSCs have tenogenic potential. Potentially shared mechanisms of cell function between MSCs and TPCs should be investigated in longer term studies.
ISSN:	1757-6512 1757-6512