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

通过 Mohawk 和三维循环机械拉伸培养系统的组合来体外新发生肌腱 / 韧带样组织。

• 影响指数: 6.081
• 发表时间: 2020
• 来源期刊: Front Cell Dev Biol
• DOI: 10.3389/fcell.2020.00307
• PMID: 32671057
• 文章类型: Journal Article
• 作者列表: 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 MK,Naruse K,Asahara H

关键词: Mohawk; ligament; mechanical-stress; tendon; tissue engineering

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.

摘要

肌腱和韧带是紧密连接肌肉和骨骼的关键结缔组织。在这项研究中,我们开发了一种新的方法来产生具有分层结构的肌腱/韧带样组织，通过将腱/韧带特异性转录因子Mohawk（MKX）引入间充质干细胞（MSC）系C3H10T1/2细胞，并通过应用改进的三维（3D）循环机械拉伸培养系统。在我们开发的协议中，稳定的Mkx表达和周期性机械拉伸的组合协同影响结构肌腱/韧带样组织的产生和肌腱相关基因表达。在这些肌腱/韧带样组织的组织学分析中，有组织的细胞外基质（ECM），含有III型胶原蛋白和弹性蛋白，被观察到。此外，我们证实了Mkx表达和循环机械拉伸，诱导了在我们的肌腱/韧带样组织生成过程中以纤维状方式沉积的结构胶原原纤维束的排列。我们的发现为肌腱/韧带生物材料领域提供了新的见解。