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

Stem Cell Res Ther. 2015 May 9;6(1):89. doi: 10.1186/s13287-015-0043-z.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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 Type I / genetics
  • Collagen Type I / metabolism
  • Down-Regulation / drug effects
  • 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*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Transgenic
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Tendons / cytology*
  • Tensile Strength*
  • Transcriptome / drug effects
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / metabolism
  • Transforming Growth Factor beta2 / pharmacology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Collagen Type I
  • Fibroblast Growth Factor 4
  • Membrane Proteins
  • Recombinant Proteins
  • Scx protein, mouse
  • Tnmd protein, mouse
  • Transforming Growth Factor beta2
  • Elastin