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Home / Equine Research Bank / Tissue Eng Part A / Three-dimensional culture and transforming growth factor bet...
Tissue engineering. Part A2014; 20(19-20); 2604-2613; doi: 10.1089/ten.TEA.2013.0457

Three-dimensional culture and transforming growth factor beta3 synergistically promote tenogenic differentiation of equine embryo-derived stem cells.

Abstract: The natural reparative mechanisms triggered by tendon damage often lead to the formation of biomechanically inferior scar tissue that is prone to re-injury. Before the efficient application of stem cell-based regenerative therapies, the processes regulating tenocyte differentiation should first be better understood. Three-dimensional (3D) growth environments under strain and the exogenous addition of transforming growth factor beta3 (TGF-β3) have separately been shown to promote tendon differentiation. The aim of this study was to determine the ability of both of these factors to induce tendon differentiation of equine embryo-derived stem cells (ESCs). ESCs seeded into 3D collagen constructs can contract the matrix to a similar degree to that of tenocyte-seeded constructs and histologically appear nearly identical, with no areas of cartilage or bone tissue deposition. Tendon-associated genes and proteins Tenascin-C, Collagen Type I, and COMP are significantly up-regulated in the 3D ESC constructs compared with tenogenic induction in monolayer ESC cultures. The addition of TGF-β3 to the 3D cultures further up-regulates the expression of these genes and also induces the expression of mature tenocyte markers Tenomodulin and Thrombospondin-4. Our results show that when ESCs are exposed to the intrinsic forces exerted by a 3D culture environment, they express tendon-associated genes and proteins which are indicative of tenocyte lineage differentiation and that this effect is synergistically enhanced and accelerated by the addition of TGF-β3.
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Publication Date: 2014-04-21 PubMed ID: 24628376PubMed Central: PMC4195467DOI: 10.1089/ten.TEA.2013.0457Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the synergistic effect of three-dimensional cell culture and transforming growth factor beta3 in encouraging tendon-like behavior in horse stem cells. The goal is to achieve better understanding of tenocyte development, which may lead to more effective stem-cell related treatments for tendon injuries.

Research Objective

  • The main aim of this research was to examine how three-dimensional (3D) cell growth environments under strain and the external addition of transforming growth factor beta3 (TGF-β3) influenced the transformation of equine embryo-derived stem cells (ESCs) into tendon-like cells (tenocytes).

Study Design and Findings

  • The researchers analyzed equine ESCs cultured in a 3D collagen matrix setup which mimics the natural physical environment for tendon development.
  • It was found that ESCs in this 3D setup were able to strain the collagen matrix to similar degrees as actual tenocytes, indicating a successful transformation.
  • The 3D grown ESCs showed upregulated levels of tendon-associated genes and proteins which are characteristic of tenocyte lineage.
  • Adding TGF-β3 to the 3D culture further triggered the expression of these tendon-associated markers, implying a synergistic effect between the simulated 3D growth environment and the addition of TGF-β3.

Implications of the Study

  • The research results suggest that exposing ESCs in a 3D culture setup to TGF-β3 can accelerate the shift towards tenocyte lineage – a necessary step forward in improving stem-cell therapy strategies for healing tendon injuries.
  • This deeper understanding of tenocyte development could lead to the formation of a biomechanically robust tissue instead of inferior-quality scar tissue during the natural healing process, thus reducing the risk of recurrent injuries.

Cite This Article

APA
Barsby T, Bavin EP, Guest DJ. (2014). Three-dimensional culture and transforming growth factor beta3 synergistically promote tenogenic differentiation of equine embryo-derived stem cells. Tissue Eng Part A, 20(19-20), 2604-2613. https://doi.org/10.1089/ten.TEA.2013.0457

Publication

Tissue engineering. Part A
ISSN: 1937-335X
NlmUniqueID: 101466659
Country: United States
Language: English
Volume: 20
Issue: 19-20
Pages: 2604-2613

Researcher Affiliations

Barsby, Tom
  • Animal Health Trust, Centre for Preventive Medicine , Newmarket, Suffolk, United Kingdom .
Bavin, Emma P
    Guest, Debbie J

      MeSH Terms

      • Animals
      • Antigens, Differentiation / biosynthesis
      • Cell Culture Techniques / methods
      • Cell Differentiation / drug effects
      • Cells, Cultured
      • Embryonic Stem Cells / cytology
      • Embryonic Stem Cells / metabolism
      • Gene Expression Regulation / drug effects
      • Horses
      • Tendons / cytology
      • Tendons / metabolism
      • Transforming Growth Factor beta3 / pharmacology

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