Mechanical stretch induces hair regeneration through the alternative activation of macrophages

Szu Ying Chu, Chih Hung Chou, Hsien Da Huang, Meng Hua Yen, Hsiao Chin Hong, Po Han Chao, Yu Hsuan Wang, Po Yu Chen, Shi Xin Nian, Yu Ru Chen, Li Ying Liou, Yu Chen Liu, Hui Mei Chen, Feng Mao Lin, Yun Ting Chang, Chih Chiang Chen*, Oscar K. Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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.

Original languageEnglish
Article number1524
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2019


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