Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair

Lan Ma; Chider Chen; Dawei Liu; Zhiqing Huang; Jiaqi Li; Haixiang Liu; Ryan Tsz Kin Kwok; Benzhong Tang; Bingdong Sui; Xiao Zhang; Jianxia Tang; Xueli Mao; Weiying Huang; Songtao Shi; Xiaoxing Kou

doi:10.1016/j.bioactmat.2022.04.022

Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair

Bioact Mater. 2022 May 11:19:626-641. doi: 10.1016/j.bioactmat.2022.04.022. eCollection 2023 Jan.

Authors

Lan Ma^{1

2}, Chider Chen², Dawei Liu^{2

3}, Zhiqing Huang¹, Jiaqi Li¹, Haixiang Liu⁴, Ryan Tsz Kin Kwok⁴, Benzhong Tang⁵, Bingdong Sui^{1

2}, Xiao Zhang^{1

2}, Jianxia Tang^{1

2}, Xueli Mao¹, Weiying Huang¹, Songtao Shi^{1

2

6}, Xiaoxing Kou^{1

2

6}

Affiliations

¹ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, 510055, Guangzhou, China.
² Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA, 19104, USA.
³ Department of Orthodontics, Peking University School & Hospital of Stomatology, #22 Zhongguancun South Avenue, Beijing, 100081, China.
⁴ Department of Chemical and Biological Engineering, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
⁵ Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Boulevard, Longgang District, Shenzhen City, Guangdong, 518172, China.
⁶ Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, 510055, China.

Abstract

Over 300 billion of cells die every day in the human body, producing a large number of endogenous apoptotic extracellular vesicles (apoEVs). Also, allogenic stem cell transplantation, a commonly used therapeutic approach in current clinical practice, generates exogenous apoEVs. It is well known that phagocytic cells engulf and digest apoEVs to maintain the body's homeostasis. In this study, we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles. Mechanistically, apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern. The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension, which is associated with the mechanical force-regulated expression of DKK1 in circulation. Furthermore, we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells. This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.

Keywords: Apoptosis; Extracellular vesicle; Integumentary system; Mesenchymal stem cells; Metabolized regulator.