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Tenogenic differentiation of human embryonic stem cells

Dale, Tina P.; Mazher, Shazia; Webb, William R.; Zhou, Jing; Maffulli, Nicola; Chen, Guo-Qiang; El Haj, Alicia J.; Forsyth, Nicholas R.

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Authors

Shazia Mazher

William R. Webb

Jing Zhou

Nicola Maffulli

Guo-Qiang Chen

Alicia J. El Haj

Nicholas R. Forsyth



Abstract

Tendon healing is complex to manage because of the limited regeneration capacity of tendon tissue; stem cell-based tissue engineering approaches may provide alternative healing strategies. We sought to determine whether human embryonic stem cells (hESC) could be induced to differentiate into tendon-like cells by the addition of exogenous bone morphogenetic protein (BMP)12 (growth differentiation factor[GDF]7) and BMP13 (GDF6). hESC (SHEF-1) were maintained with or without BMP12/13 supplementation, or supplemented with BMP12/13 and the Smad signaling cascade blocking agent, dorsomorphin. Primary rat tenocytes were included as a positive control in immunocytochemistry analysis. A tenocyte-like elongated morphology was observed in hESC after 40-days continuous supplementation with BMP12/13 and ascorbic acid (AA). These cells displayed a tenomodulin expression pattern and morphology consistent with that of the primary tenocyte control. Analysis of tendon-linked gene transcription in BMP12/13 supplemented hESC demonstrated consistent expression of COL1A2, COL3A1, DCN, TNC, THBS4, and TNMD levels. Conversely, when hESCs were cultured in the presence of BMP12/13 and dorsomorphin COL3A1, DCN, and TNC gene expression and tendon matrix formation were inhibited. Taken together, we have demonstrated that hESCs are responsive to tenogenic induction via BMP12/13 in the presence of AA. The directed in vitro generation of tenocytes from pluripotent stem cells may facilitate the development of novel repair approaches for this difficult to heal tissue.

Journal Article Type Article
Acceptance Date Jan 9, 2017
Publication Date Mar 1, 2018
Publicly Available Date Mar 29, 2024
Journal Tissue Engineering: Parts A, B, and C
Print ISSN 1937-3341
Publisher Mary Ann Liebert
Peer Reviewed Peer Reviewed
Volume 24
Issue 5-6
Pages 361-368
DOI https://doi.org/10.1089/ten.TEA.2017.0017
Publisher URL http://online.liebertpub.com/doi/abs/10.1089/ten.TEA.2017.0017?journalCode=tea

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