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The relationship between substrate topography and stem cell differentiation in the musculoskeletal system

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Abstract

It is well known that biomaterial topography can exert a profound influence on various cellular functions such as migration, polarization, and adhesion. With the development and refinement of manufacturing technology, much research has recently been focused on substrate topography-induced cell differentiation, particularly in the field of tissue engineering. Even without biological and chemical stimuli, the differentiation of stem cells can also be initiated by various biomaterials with different topographic features. However, the underlying mechanisms of this biological phenomenon remain elusive. During the past few decades, many researchers have demonstrated that cells can sense the topography of materials through the assembly and polymerization of membrane proteins. Following the activation of RHO, TGF-b or FAK signaling pathways, cells can be induced into various differentiation states. But these signaling pathways often coincide with canonical mechanical transduction pathways, and no firm conclusion has been reached among researchers in this field on topography-specific signaling pathways. On the other hand, some substrate topographies are reported to have the ability to inhibit differentiation and maintain the ‘stemness’ of stem cells. In this review, we will summarize the role of topography in musculoskeletal system regeneration and explore possible topography-related signaling pathways involved in cell differentiation.

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Acknowledgements

This work of our research group was supported by the National key R&D program of China (2017YFA0104901, 2017YFA0104900), National key research and development program of China (2016YFC1100204), NSFC Grants (81572115, 81874019, 81572157, 81330041, 81125014, 31271041, 81201396, 81271970, J1103603, 81522029, 31570987, 81401781), Regenerative Medicine in Innovative Medical Subjects of Zhejiang Province and Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents, Zhejiang Province Grants (Z2100086, LY12H06006, LR14H060001, LY14H060003), the Key scientific and technological innovation team of Zhejiang Province (2013TD11), Medical and Health Science and Technology Plan of the Department of Health of Zhejiang Province (2013RCA010, 2014KYB052), Medical Science and Technology Project of Zhejiang Province (201341741), and Zhejiang Provisional Grant (2012C33015). International Science and Technology Cooperation Program of China (2015DFG32130). Fundamental Research Funds for the Central Universities. None of the authors had professional or financial affiliations that biased this work.

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  1. Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310009, China

    Jiayun Huang, Yangwu Chen, Chenqi Tang, Yang Fei, Dengfeng Ruan, Weishan Chen & Weiliang Shen

  2. Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Zhejiang, 310000, China

    Jiayun Huang, Yangwu Chen, Chenqi Tang, Haoyu Wu, Maswikiti Ewetse Paul, Xiao Chen, Zi Yin & Weiliang Shen

  3. Orthopaedics Research Institute of Zhejiang University, Zhejiang, China

    Jiayun Huang, Yangwu Chen, Chenqi Tang, Yang Fei, Dengfeng Ruan & Weiliang Shen

  4. Department of Sports Medicine, School of Medicine, Zhejiang University, Zhejiang, 310000, China

    Jiayun Huang, Yangwu Chen, Chenqi Tang, Haoyu Wu, Maswikiti Ewetse Paul, Xiao Chen, Zi Yin & Weiliang Shen

  5. Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

    Boon Chin Heng

  6. China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China

    Jiayun Huang, Yangwu Chen, Chenqi Tang, Yang Fei, Dengfeng Ruan, Xiao Chen & Weiliang Shen

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  1. Jiayun Huang
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Huang, J., Chen, Y., Tang, C. et al. The relationship between substrate topography and stem cell differentiation in the musculoskeletal system. Cell. Mol. Life Sci. 76, 505–521 (2019). https://doi.org/10.1007/s00018-018-2945-2

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  • DOI: https://doi.org/10.1007/s00018-018-2945-2

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