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Original Paper

Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro

Tan S.-L.a · Ahmad R.E.b · Ahmad T.S.a · Merican A.M.a · Abbas A.A.a · Ng W.M.a · Kamarul T.a

Author affiliations

aTissue Engineering Group, National Orthopaedic Centre of Excellence for Research and Learning, Department of Orthopaedic Surgery, and bDepartment of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

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Cells Tissues Organs 2012;196:325–338

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 15, 2011
Accepted: December 12, 2011
Published online: May 30, 2012
Issue release date: September 2012

Number of Print Pages: 14
Number of Figures: 6
Number of Tables: 3

ISSN: 1422-6405 (Print)
eISSN: 1422-6421 (Online)

For additional information: https://www.karger.com/CTO

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.

© 2012 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 15, 2011
Accepted: December 12, 2011
Published online: May 30, 2012
Issue release date: September 2012

Number of Print Pages: 14
Number of Figures: 6
Number of Tables: 3

ISSN: 1422-6405 (Print)
eISSN: 1422-6421 (Online)

For additional information: https://www.karger.com/CTO


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