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Nat Commun. 2019 Apr 3;10(1):1524. doi: 10.1038/s41467-019-09402-8.

Mechanical stretch induces hair regeneration through the alternative activation of macrophages.

Chu SY1,2,3, Chou CH4, Huang HD5, Yen MH6, Hong HC7, Chao PH2, Wang YH8,9, Chen PY1,3, Nian SX1,3, Chen YR2, Liou LY1,3, Liu YC7, Chen HM7, Lin FM7, Chang YT1,3, Chen CC10,11,12, Lee OK13,14,15.

Author information

1
Department of Dermatology, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
2
Institute of Clinical Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
3
Department of Dermatology, National Yang-Ming University, Taipei, 112, Taiwan.
4
Department of Biological Science and Technology, Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Chiao Tung University, Hsinchu, 300, Taiwan.
5
Warshel Institute for Computational Biology, School of Life and Health Sciences, School of Sciences and Engineering, The Chinese University of Hong Kong, Shenzhen, 518172, China.
6
Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, 411, Taiwan.
7
Department of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 300, Taiwan.
8
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, 999077, China.
9
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong, 999077, China.
10
Department of Dermatology, Taipei Veterans General Hospital, Taipei, 112, Taiwan. docs1.tw@yahoo.com.tw.
11
Institute of Clinical Medicine, National Yang-Ming University, Taipei, 112, Taiwan. docs1.tw@yahoo.com.tw.
12
Department of Dermatology, National Yang-Ming University, Taipei, 112, Taiwan. docs1.tw@yahoo.com.tw.
13
Institute of Clinical Medicine, National Yang-Ming University, Taipei, 112, Taiwan. oscarlee9203@gmail.com.
14
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, 999077, China. oscarlee9203@gmail.com.
15
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong, 999077, China. oscarlee9203@gmail.com.

Abstract

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.

PMID:
30944305
PMCID:
PMC6447615
DOI:
10.1038/s41467-019-09402-8
[Indexed for MEDLINE]
Free PMC Article

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