Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2025; 17(3): 102088
Published online Mar 26, 2025. doi: 10.4252/wjsc.v17.i3.102088
Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia
Yu Fu, Yao-Ting Han, Jun-Ling Xie, Rong-Qi Liu, Bo Zhao, Xing-Liao Zhang, Jun Zhang, Jing Zhang
Yu Fu, Yao-Ting Han, Rong-Qi Liu, Bo Zhao, Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
Jun-Ling Xie, Xing-Liao Zhang, Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
Jun Zhang, Jing Zhang, Tongji Lifeng Institute of Regenerative Medicine, Tongji University, Shanghai 200092, China
Jun Zhang, Research Center for Translational Medicine at East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, School of Medicine, Tongji University, Shanghai 200092, China
Jing Zhang, Research Center for Translational Medicine at East Hospital, School of Life Science, Tongji University, Shanghai 200092, China
Co-first authors: Yu Fu and Yao-Ting Han.
Co-corresponding authors: Jun Zhang and Jing Zhang.
Author contributions: Zhang J and Zhang J mainly designed and led the process of the project and as co-corresponding authors of this manuscript. Fu Y and Han YT wrote the manuscript and contributed equally to this manuscript as co-first authors of this manuscript. Fu Y, Xie JL, Liu RQ, Zhao B, and Zhang XL performed the experiments; Fu Y, Xie JL, Zhao B, and Zhang XL analyzed the data; Fu Y, Han YT, and Liu RQ performed statistical analysis. All authors read and approved the final manuscript.
Supported by the Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai and the China Postdoctoral Science Foundation, No. 2022M722409.
Institutional review board statement: The study protocol conformed to the Declaration of Helsinki and was approved by the Committee of Ethics on Experimentation of Tongji University (Shanghai, China), approval No. [2024]094.
Institutional animal care and use committee statement: This study was approved by Tongji University, with the ethics approval No. TJAA09524102.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data can be supplied for reasonable requests.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Zhang, PhD, Professor, Research Center for Translational Medicine at East Hospital, School of Life Science, Tongji University, No. 1239 Siping Road, Shanghai 200092, China. 96755@tongji.edu.cn
Received: October 9, 2024
Revised: January 21, 2025
Accepted: February 26, 2025
Published online: March 26, 2025
Processing time: 163 Days and 3.5 Hours
Abstract
BACKGROUND

Mesenchymal stem cells (MSCs) and their secretome have significant potential in promoting hair follicle development. However, the effects of MSC therapy have been reported to vary due to their heterogeneous characteristics. Different sources of MSCs or culture systems may cause heterogeneity of exosomes.

AIM

To define the potential of human adipose-derived MSC exosomes (hADSC-Exos) and human umbilical cord-derived MSC exosomes (hUCMSC-Exos) for improving dermal papillary cell proliferation in androgenetic alopecia.

METHODS

We conducted liquid chromatography-mass spectrometry proteomic analysis of hADSC-Exos and hUCMSC-Exos. Liquid chromatography-mass spectrometry suggested that hADSC-Exos were related to metabolism and immunity. Additionally, the hADSC-Exo proteins regulated the cell cycle and other 9 functional groups.

RESULTS

We verified that hADSC-Exos inhibited glycogen synthase kinase-3β expression by activating the Wnt/β-catenin signaling pathway via cell division cycle protein 42, and enhanced dermal papillary cell proliferation and migration. Excess dihydrotestosterone caused androgenetic alopecia by shortening the hair follicle growth phase, but hADSC-Exos reversed these effects.

CONCLUSION

This study indicated that hair development is influenced by hADSC-Exo-mediated cell-to-cell communication via the Wnt/β-catenin pathway.

Keywords: Mesenchymal stem cells; Exosome; Dermal papillary cells; Hair development; Liquid chromatography-mass spectrometry proteomic analysis

Core Tip: Liquid chromatography-mass spectrometry proteomic analysis was conducted to reveal the commonalities and heterogeneities across the human adipose-derived mesenchymal stem cell exosomes (hADSC-Exos) and human umbilical cord-derived mesenchymal stem cell exosomes. A total of 232 common proteins were found in hADSC-Exos and were categorized into 10 functional groups. We have confirmed that hADSC-Exos decrease glycogen synthase kinase-3β expression through the Wnt/β-catenin pathway, leading to increased proliferation and migration of dermal papillary cell. Excessive dihydrotestosterone can cause hair loss by shortening the hair growth phase, but hADSC-Exo treatment can reverse this effect. This study suggests that hADSC-Exo plays a role in hair regeneration through cell-to-cell communication via the Wnt/β-catenin pathway.