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  Growth factor-mediated tenogenic induction of multipotent mesenchymal stromal cells is altered by the microenvironment of tendon matrix

Roth, S. P., Schubert, S., Scheibe, P., Groß, C., Brehm, W., & Burk, J. (2018). Growth factor-mediated tenogenic induction of multipotent mesenchymal stromal cells is altered by the microenvironment of tendon matrix. Cell Transplantation, 27(10), 1434-1450. doi:10.1177/0963689718792203.

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Roth, Susanne Pauline1, 2, Author
Schubert, Susanna2, 3, Author
Scheibe, Patrick2, Author           
Groß, Claudia2, Author
Brehm, Walter1, Author
Burk, Janina1, 3, Author
1Faculty of Veterinary Medicine, Veterinary Teaching Hospital Department for Horses, University of Leipzig, Germany, ou_persistent22              
2Saxonian Incubator for Clinical Translation (SIKT), University of Leipzig, Germany, ou_persistent22              
3Institute of Veterinary Physiology, University of Leipzig, Germany, ou_persistent22              


Free keywords: Cell therapy; Tissue engineering; Tendon; Horse; Multipotent mesenchymal stromal cells (MSC); Transforming growth factor beta 3 (TGFβ3)
 Abstract: Age-related degenerative changes in tendon tissue represent a common cause for acute tendon pathologies. Although the regenerative potential of multipotent mesenchymal stromal cells (MSC) was reported to restore functionality in injured tendon tissue, cellular mechanisms of action remain partly unclear. Potential tenogenic differentiation of applied MSC is affected by various intrinsic and extrinsic factors. The current study presents an in vitro model to evaluate the combined extrinsic effects of decellularized equine tendon matrix, transforming growth factor beta 3 (TGFβ3) and bone morphogenetic protein 12 (BMP12) on the tenogenic fate of equine adipose tissue-derived MSC. Monolayer MSC cultures supplemented with TGFβ3 and BMP12 as well as MSC cultured on tendon matrix scaffolds preloaded with the growth factors were incubated for 3 and 5 days. Histological evaluation and real time reverse transcription polymerase chain reaction (RT-PCR) revealed that growth factor-mediated tenogenic induction of MSC was modified by the conditions of the surrounding microenvironment. While the gene expression pattern in monolayer cultures supplemented with TGFβ3 or TGFβ3 and BMP12 revealed an upregulation for collagen 1A2, collagen 3A1, tenascin c, scleraxis and mohawk (p < 0.05), the presence of tendon matrix led to an upregulation of decorin and osteopontin as well as to a downregulation of smad8 (p < 0.05). Preloading of scaffolds with either TGFβ3, or with TGFβ3 and BMP12 promoted a tenocyte-like phenotype and improved cell alignment. Furthermore, gene expression in scaffold culture was modulated by TGFβ3 and/or BMP12, with downregulation of collagen 1A2, collagen 3A1, decorin, scleraxis, smad8 and osteopontin, whereas gene expression of tenascin c was increased. This study shows that growth factor-induced tenogenic differentiation of equine MSC is markedly altered by topographical constraints of decellularized tendon tissue in vitro. While TGFβ3 represents an effective mediator for tenogenic induction, the role of BMP12 in tenogenesis may be of modulatory character and needs further evaluation.


Language(s): eng - English
 Dates: 2018-09-252018-10-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1177/0963689718792203
Other: Epub 2018
PMID: 30251565
PMC: PMC6180728
 Degree: -



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Project name : -
Grant ID : 1315883
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : -
Grant ID : BU3110/1-1
Funding program : -
Funding organization : German National Research Foundation (DFG)

Source 1

Title: Cell Transplantation
  Other : Cell Transplant.
Source Genre: Journal
Publ. Info: Elmsford, NY : No longer published by Elsevier
Pages: - Volume / Issue: 27 (10) Sequence Number: - Start / End Page: 1434 - 1450 Identifier: ISSN: 0963-6897
CoNE: https://pure.mpg.de/cone/journals/resource/954925580138