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Mechanical and Topographical Guidance of Stem Cell Differentiation in Vitro Via YAP-Dependent Mechanotransduction: A Biomimetic Approach Toward Annulus Fibrosus Regeneration

29 Pages Posted: 22 Jan 2019 First Look: Under Review

See all articles by Genglei Chu

Genglei Chu

Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute

Zhangqin Yuan

Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute

Pinghui Zhou

Bengbu Medical College - Department of Orthopaedic Surgery

Caihong Zhu

Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute

Weidong Zhang

Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute

Huan Wang

Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute

Huilin Yang

Soochow University - Department of Orthopedics; Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute

Bin Li

Soochow University - Department of Orthopaedic Surgery; Soochow University - Orthopaedic Institute; China Orthopaedic Regenerative Medicine Group (CORMed)

Abstract

The current engineered bionic disc tissue is considered as a potential way for treating intervertebral disc degeneration disease, which yet still remains challenging due to the complex radial gradient of natural annulus fibrosus (AF) tissue in cell phenotype, biochemical composition, topographical features, and mechanical properties. Previously, we have found that the differentiation of annulus fibrosus-derived stem cells (AFSCs) could be regulated by the elasticity of scaffold. In this study, we attempted to examine the combined effect of both mechanical and topographical features on the gene expression of AFSCs. Cells were cultured on four types of poly(ether carbonate urethane) urea (PECUU) scaffolds with controlled elasticity and fiber size (soft, small size; stiff, small size; soft, large size and stiff, large size). Results showed that when the fiber size of scaffold was kept constant, the expression of collagen-I (Col-I) in AFSCs increased with scaffold elasticity, while the expression of collagen-II (Col-II) and aggrecan genes showed an opposite trend. Moreover, when scaffold elasticity was controlled, the gene expression of Col-I in AFSCs increased with fiber size. In contrast, the expression of Col-II and aggrecan decreased. Such substrate elasticity and topography dependent changes of AFSC were similar to the gradient characteristics of native AF tissue. In addition, increasing elasticity and fiber size of scaffolds promoted YAP activation and its nuclear translocation. The results illustrate unambiguously that the mechanical property is a potent regulator of AFSC differentiation. Moreover, we revealed that fiber size of scaffold significantly affects spreading area, focal adhesion and differentiation of AFSCs. Therefore, both mechanical property and topography features of scaffolds regulate AFSC differentiation, possibly through a YAP-dependent mechanotransduction mechanism.

Keywords: rabbit annulus-derived stem cell, mechanical property, topography, differentiation, regulation, electrospun, polyurethane fibre scaffold;YAP

Suggested Citation

Chu, Genglei and Yuan, Zhangqin and Zhou, Pinghui and Zhu, Caihong and Zhang, Weidong and Wang, Huan and Yang, Huilin and Li, Bin, Mechanical and Topographical Guidance of Stem Cell Differentiation in Vitro Via YAP-Dependent Mechanotransduction: A Biomimetic Approach Toward Annulus Fibrosus Regeneration (January 18, 2019). Available at SSRN: https://ssrn.com/abstract=3318387 or http://dx.doi.org/10.2139/ssrn.3318387

Genglei Chu (Contact Author)

Soochow University - Department of Orthopaedic Surgery

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Zhangqin Yuan

Soochow University - Department of Orthopaedic Surgery

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Pinghui Zhou

Bengbu Medical College - Department of Orthopaedic Surgery

China

Caihong Zhu

Soochow University - Department of Orthopaedic Surgery

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Weidong Zhang

Soochow University - Department of Orthopaedic Surgery

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Huan Wang

Soochow University - Department of Orthopaedic Surgery

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Huilin Yang

Soochow University - Department of Orthopedics ( email )

China

Soochow University - Department of Orthopaedic Surgery ( email )

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute ( email )

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Bin Li

Soochow University - Department of Orthopaedic Surgery ( email )

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Soochow University - Orthopaedic Institute ( email )

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

China Orthopaedic Regenerative Medicine Group (CORMed) ( email )

Hangzhou, Zhejiang
China

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