title: Cyclic Tensile Strain Induces Tenogenic Differentiation of Tendon-Derived Stem Cells in Bioreactor Culture.
abstract: Different loading regimens of cyclic tensile strain impose different effects on cell proliferation and tenogenic differentiation of TDSCs in three-dimensional (3D) culture in vitro, which has been little reported in previous literatures. In this study we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation in the custom-designed 3D tensile bioreactor, which revealed that cyclic tensile strain with different frequencies (0.3 Hz, 0.5 Hz, and 1.0 Hz) and amplitudes (2%, 4%, and 8%) had no influence on TDSC viability, while it had different effects on the proliferation and the expression of type I collagen, tenascin-C, tenomodulin, and scleraxis of TDSCs, which was most obvious at 0.5 Hz frequency with the same amplitude and at 4% amplitude with the same frequency. Moreover, signaling pathway from microarray analysis revealed that reduced extracellular matrix (ECM) receptor interaction signaling initiated the tendon genius switch. Cyclic tensile strain highly upregulated genes encoding regulators of NPM1 and COPS5 transcriptional activities as well as MYC related transcriptional factors, which contributed to cell proliferation and differentiation. In particular, the transcriptome analysis provided certain new insights on the molecular and signaling networks for TDSCs loaded in these conditions.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China ; Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D008297:Male; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*