In vitro Neo-Genesis of Tendon/Ligament-Like Tissue by Combination of Mohawk and a Three-Dimensional Cyclic Mechanical Stretch Culture System

Kensuke Kataoka, Ryota Kurimoto, Hiroki Tsutsumi, Tomoki Chiba, Tomomi Kato, Kana Shishido, Mariko Kato, Yoshiaki Ito, Yuichiro Cho, Osamu Hoshi, Ayako Mimata, Yuriko Sakamaki, Ryo Nakamichi, Martin K. Lotz, Keiji Naruse, Hiroshi Asahara

Research output: Contribution to journalArticle

Abstract

Tendons and ligaments are pivotal connective tissues that tightly connect muscle and bone. In this study, we developed a novel approach to generate tendon/ligament-like tissues with a hierarchical structure, by introducing the tendon/ligament-specific transcription factor Mohawk (MKX) into the mesenchymal stem cell (MSC) line C3H10T1/2 cells, and by applying an improved three-dimensional (3D) cyclic mechanical stretch culture system. In our developed protocol, a combination of stable Mkx expression and cyclic mechanical stretch synergistically affects the structural tendon/ligament-like tissue generation and tendon related gene expression. In a histological analysis of these tendon/ligament-like tissues, an organized extracellular matrix (ECM), containing collagen type III and elastin, was observed. Moreover, we confirmed that Mkx expression and cyclic mechanical stretch, induced the alignment of structural collagen fibril bundles that were deposited in a fibripositor-like manner during the generation of our tendon/ligament-like tissues. Our findings provide new insights for the tendon/ligament biomaterial fields.

Original languageEnglish
Article number307
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - Jun 2 2020

Keywords

  • Mohawk
  • ligament
  • mechanical-stress
  • tendon
  • tissue engineering

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Kataoka, K., Kurimoto, R., Tsutsumi, H., Chiba, T., Kato, T., Shishido, K., Kato, M., Ito, Y., Cho, Y., Hoshi, O., Mimata, A., Sakamaki, Y., Nakamichi, R., Lotz, M. K., Naruse, K., & Asahara, H. (2020). In vitro Neo-Genesis of Tendon/Ligament-Like Tissue by Combination of Mohawk and a Three-Dimensional Cyclic Mechanical Stretch Culture System. Frontiers in Cell and Developmental Biology, 8, [307]. https://doi.org/10.3389/fcell.2020.00307