Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2022; 14(7): 527-538
Published online Jul 26, 2022. doi: 10.4252/wjsc.v14.i7.527
Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles
Ramya Lakshmi Rajendran, Prakash Gangadaran, Mi Hee Kwack, Ji Min Oh, Chae Moon Hong, Young Kwan Sung, Jaetae Lee, Byeong-Cheol Ahn
Ramya Lakshmi Rajendran, Prakash Gangadaran, Ji Min Oh, Chae Moon Hong, Jaetae Lee, Byeong-Cheol Ahn, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Prakash Gangadaran, Mi Hee Kwack, Young Kwan Sung, Byeong-Cheol Ahn, BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Mi Hee Kwack, Young Kwan Sung, Department of Immunology, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
Chae Moon Hong, Jaetae Lee, Byeong-Cheol Ahn, Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, South Korea
Author contributions: Rajendran RL and Gangadaran P contributed equally to this study; Rajendran RL, Gangadaran P and Ahn BC contributed to the conception and design of the study, data interpretation, and funding acquisition; Rajendran RL, Gangadaran P, Kwack MH, Oh JM and Hong CM contributed to the methodology, data acquisition, and analysis; Rajendran RL and Gangadaran P wrote the original draft of the article; Kwack MH, Oh JM, Hong CM, Sung YK and Lee J drafted, reviewed and edited the manuscript, and contributed to project administration; The study was led by Ahn BC, and all of the authors read and approved the final version of the manuscript.
Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), Funded by the Ministry of Education, No. NRF-2019R1I1A1A01061296 and No. NRF-2021R1I1A1A01040732; Korea Health Technology R & D Project through the Korea Health Industry Development Institute, Funded By the Ministry of Health & Welfare, Republic of Korea, No. HI15C0001.
Institutional review board statement: This study was approved by the Institutional Review Board (IRB) of Kyungpook National University Hospital, No. KNU-2018-0161 and conducted in accordance with the principles of the Declaration of Helsinki.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Byeong-Cheol Ahn, MD, PhD, Professor, Department of Nuclear Medicine, School of Medicine, Kyungpook National University, No. 680 Gukchaebosangro, Junggu, Daegu 41944, South Korea. abc2000@knu.ac.kr
Received: March 4, 2022
Peer-review started: March 4, 2022
First decision: April 19, 2022
Revised: May 19, 2022
Accepted: June 24, 2022
Article in press: June 24, 2022
Published online: July 26, 2022
Processing time: 144 Days and 4.2 Hours
Abstract
BACKGROUND

Dermal papillae (DP) and outer root sheath (ORS) cells play important roles in hair growth and regeneration by regulating the activity of hair follicle (HF) cells.

AIM

To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) on DP and ORS cells as well as HFs. EVs are known to regulate various cellular functions. However, the effects of hMSC-EVs on hair growth, particularly on human-derived HF cells (DP and ORS cells), and the possible mechanisms underlying these effects are unknown.

METHODS

hMSC-EVs were isolated and characterized using transmission electron microscopy, nanoparticle tracking analysis, western blotting, and flow cytometry. The activation of DP and ORS cells was analyzed using cellular proliferation, migration, western blotting, and real-time polymerase chain reaction. HF growth was evaluated ex vivo using human HFs.

RESULTS

Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane. hMSC-EVs promote the proliferation of DP and ORS cells. Moreover, they translocate β-catenin into the nucleus of DP cells by increasing the expression of β-catenin target transcription factors (Axin2, EP2 and LEF1) in DP cells. Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin (K) differentiation markers (K6, K16, K17, and K75) in ORS cells. Furthermore, treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs.

CONCLUSION

These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.

Keywords: Mesenchymal stem cells; Extracellular vesicles; Hair growth; Dermal papillae; Outer root sheath cells

Core Tip: Alopecia is a common medical problem affecting both males and females. This study found that Wnt3a is enriched in human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) and associated with their EVs’ surface. hMSC-EVs associated wnt3a can activate the Wnt/β-catenin signaling in recipient dermal papillae cells. hMSC-EVs activate keratin differentiation in recipient outer root sheath cells and increase hair shaft elongation. These findings open up for new hair growth treatment strategies to be developed for alopecia.