Mesenchymal stem cell-derived exosomes and the Wnt/β-catenin pathway: Unifying mechanisms of multi-organ regeneration and the path to precision clinical translation.

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.