Yan X, Guo YX, Liu YX, Liu C. Mesenchymal stem cell-derived exosomes and the Wnt/β-catenin pathway: Unifying mechanisms of multi-organ regeneration and the path to precision clinical translation. World J Stem Cells 2025; 17(6): 106902 [DOI: 10.4252/wjsc.v17.i6.106902]
Corresponding Author of This Article
Chun Liu, Chief Physician, Consultant, Dean, Professor, The First Clinical Medical School, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, Shanxi Province, China. sxtyliuchun@126.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Jun 26, 2025; 17(6): 106902 Published online Jun 26, 2025. doi: 10.4252/wjsc.v17.i6.106902
Mesenchymal stem cell-derived exosomes and the Wnt/β-catenin pathway: Unifying mechanisms of multi-organ regeneration and the path to precision clinical translation
Xiong Yan, Ya-Xiong Guo, Yu-Xiang Liu, Chun Liu
Xiong Yan, Chun Liu, The First Clinical Medical School, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Ya-Xiong Guo, Surgical Unit 1, Shanxi Combined Traditional Chinese and Western Medicine Hospital, Taiyuan 030072, Shanxi Province, China
Yu-Xiang Liu, Department of Nephrology, Shanxi Provincial People’s Hospital, Taiyuan 030012, Shanxi Province, China
Co-corresponding authors: Yu-Xiang Liu and Chun Liu.
Author contributions: Liu C designed the overall concept and outline of the manuscript; Yan X and Guo YX contributed to the discussion and design of the manuscript, and to the writing; Liu YX translated the manuscript, and made preliminary revisions to the manuscript. Liu C and Liu YX contributed equally to this work and share co-corresponding authorship. They jointly conceived and co-drafted and critically revised the manuscript.
Supported by the Natural Science Research Project of Basic Research Program in Shanxi Province, No. 202203021221268; and the National Natural Science Foundation of China, No. 82305030.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Chun Liu, Chief Physician, Consultant, Dean, Professor, The First Clinical Medical School, Shanxi Medical University, No. 56 Xinjian South Road, Taiyuan 030001, Shanxi Province, China. sxtyliuchun@126.com
Received: March 11, 2025 Revised: March 31, 2025 Accepted: May 8, 2025 Published online: June 26, 2025 Processing time: 107 Days and 4.6 Hours
Abstract
In this editorial, we discuss the article by Fu Y et al, indicating that hair development is influenced by exosomes from human adipose-derived stem/stromal cell-mediated cell-to-cell communication via the Wnt/β-catenin pathway. In recent years, mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) have emerged as a promising cell-free therapeutic strategy due to their robust regenerative capabilities across multiple tissues. MSC-Exos are enriched with bioactive molecules, including proteins, microRNAs, and growth factors, which activate critical signaling pathways, notably the Wnt/β-catenin pathway, to promote cell proliferation, differentiation, and tissue repair. This editorial systematically examines the application of MSC-Exos in regenerating diverse tissues such as hair follicles and kidney, lung, and cardiac muscle tissue. Central to their mechanism is the activation of the Wnt/β-catenin pathway, which drives cell cycle progression (via cyclin B1/cyclin-dependent kinase 1), suppresses apoptosis (through Bcl-2/Bax modulation), and attenuates fibrosis (by inhibiting transforming growth factor-β/alpha-smooth muscle actin). The challenges related to the clinical translation of exosome-based therapies, including standardization of isolation protocols, optimization of dosing and delivery methods, and safety evaluation, are discussed. The most important challenge is standardizing isolation protocols because exosomes obtained from different sources or treatment methods are different, which leads to differences in the therapeutic effects of exosomes. Overall, MSC-Exos provide an effective cell-free strategy for tissue repair and offer a robust foundation to develop personalized regenerative medicine.
Core Tip: Mesenchymal stem cell-derived exosomes represent a novel form of cell-free therapy that operates through the activation of the Wnt/β-catenin pathway using the substances they contain, including proteins, microRNAs, and growth factors. These exosomes can stimulate cell proliferation, elicit anti-inflammatory responses, and promote the repair of multiple organs and tissues. However, the translation of these findings into clinical practice remains challenging. This is due to the need for standardization in exosome production and purification and the development of effective administration and storage methods. Additionally, concerns regarding immunogenicity and tumorigenicity complicate the translation of exosome therapy into clinical practice. Therefore, further exploration is necessary to fully assess the potential of exosome therapy as a personalized regenerative medicine approach.
