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机械压缩对琼脂糖水凝胶中人类滑膜间充质干细胞软骨形成的影响

Effects of Mechanical Compression on Chondrogenesis of Human Synovium-Derived Mesenchymal Stem Cells in Agarose Hydrogel.

作者信息

Ge Yuxiang, Li Yixuan, Wang Zixu, Li Lan, Teng Huajian, Jiang Qing

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Laboratory for Bone and Joint Disease, Model Animal Research Center, Nanjing University, Nanjing, China.

出版信息

Front Bioeng Biotechnol. 2021 Jul 19;9:697281. doi: 10.3389/fbioe.2021.697281. eCollection 2021.

Abstract

Mechanical compression is a double-edged sword for cartilage remodeling, and the effect of mechanical compression on chondrogenic differentiation still remains elusive to date. Herein, we investigate the effect of mechanical dynamic compression on the chondrogenic differentiation of human synovium-derived mesenchymal stem cells (SMSCs). To this aim, SMSCs encapsulated in agarose hydrogels were cultured in chondrogenic-induced medium with or without dynamic compression. Dynamic compression was applied at either early time-point (day 1) or late time-point (day 21) during chondrogenic induction period. We found that dynamic compression initiated at early time-point downregulated the expression level of chondrocyte-specific markers as well as hypertrophy-specific markers compared with unloaded control. On the contrary, dynamic compression applied at late time-point not only enhanced the levels of cartilage matrix gene expression, but also suppressed the hypertrophic development of SMSCs compared with unloaded controls. Taken together, our findings suggest that dynamic mechanical compression loading not only promotes chondrogenic differentiation of SMSCs, but also plays a vital role in the maintenance of cartilage phenotype, and our findings also provide an experimental guide for stem cell-based cartilage repair and regeneration.

摘要

机械压缩对软骨重塑来说是一把双刃剑,迄今为止,机械压缩对软骨生成分化的影响仍不明确。在此,我们研究了机械动态压缩对人滑膜来源间充质干细胞(SMSCs)软骨生成分化的影响。为此,将封装在琼脂糖水凝胶中的SMSCs在有或没有动态压缩的软骨生成诱导培养基中培养。在软骨生成诱导期的早期时间点(第1天)或晚期时间点(第21天)施加动态压缩。我们发现,与未加载的对照相比,在早期时间点开始的动态压缩下调了软骨细胞特异性标志物以及肥大特异性标志物的表达水平。相反,与未加载的对照相比,在晚期时间点施加的动态压缩不仅提高了软骨基质基因表达水平,还抑制了SMSCs的肥大发育。综上所述,我们的研究结果表明,动态机械压缩加载不仅促进了SMSCs的软骨生成分化,而且在维持软骨表型方面也起着至关重要的作用,我们的研究结果还为基于干细胞的软骨修复和再生提供了实验指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8eb/8327094/5f95c9768984/fbioe-09-697281-g001.jpg

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