Mesenchymal stem cells and their extracellular vesicle-based therapies in skin and hair rejuvenation: a scoping review

Age-related skin and hair deterioration causes significant psychosocial morbidity, yet current therapies lack consistent efficacy. Mesenchymal stem cells (MSCs) and their extracellular vesicle (EV)-based therapies are promising regenerative strategies, but their clinical utility remains unclear. We performed a scoping review to evaluate the therapeutic mechanisms and clinical efficacy of MSCs and their EV-related therapies in skin and hair rejuvenation and to identify evidence gaps. A literature screening of MEDLINE, Embase, and the Cochrane Library was conducted. We included preclinical and clinical studies that evaluated MSCs or MSC-derived EV-based products for treating age-related skin deterioration or hair loss. From 1,050 articles screened, 146 studies met the inclusion criteria. For skin rejuvenation, clinical evidence shows that MSCs and their EV-based therapies, particularly when combined with delivery-enhancing modalities like microneedling or fractional laser, may benefit wrinkle indices, skin elasticity, hydration, and pigmentation. For hair regeneration, administration of MSCs and EV-based products was reported to increase hair count and density, with high patient satisfaction and minimal adverse effects. Mechanistically, the data indicate the paracrine effect. Secreted growth factors (e.g., VEGF, HGF, IGF-1) modulate key signaling pathways. In skin, this involves activating the Wnt/β-catenin and TGF-β/Smad pathways to enhance collagen synthesis. In hair, regeneration is promoted through the activation of the Wnt/β-catenin and Akt/ERK pathways. While MSCs and their EVs-based therapies suggest potential therapeutic promise, especially when administered using delivery-enhancing modalities that create microtrauma (such as microneedling, derma-rollers, or fractional lasers), the clinical evidence base is constrained by heterogeneous study designs and a lack of standardization in cell/EV manufacturing and administration. This inconsistency confounds the interpretation of true efficacy. To realize the potential of MSC-based regenerative medicine, future research must prioritize the development of standardized protocols, the execution of robust, large-scale controlled trials, and the establishment of clear efficacy metrics for both skin and hair rejuvenation.