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Article
Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro
Cells Tissues Organs (2012)
  • Sik Loo Tan
  • Raja Elina Ahmad
  • Tunku Sara Ahmad
  • Azhar Mahmood Merican
  • Azlina Amir Abbas
  • Wuey Min Ng
Abstract

The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.

Keywords
  • Tendon,
  • tissue engineering,
  • cell-based therapy,
  • orthopaedics,
  • mesenchymal stem cells
Publication Date
May 30, 2012
Citation Information
Sik Loo Tan, Raja Elina Ahmad, Tunku Sara Ahmad, Azhar Mahmood Merican, et al.. "Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro" Cells Tissues Organs Vol. 196 Iss. 4 (2012)
Available at: http://works.bepress.com/tsara/10/