MSC-Derived Secretome and Exosomes in Dermatology: Mechanisms, Therapeutic Opportunities, and Scientific Challenges-A...

Mesenchymal stromal cells (MSCs) exert their effects primarily through paracrine signaling via soluble factors and extracellular vesicles (EVs), especially exosomes. These acellular components offer regenerative and immunomodulatory benefits with fewer safety and logistical constraints than cell-based therapies. This study aims to review the composition, mechanisms of action, and dermatologic applications of MSC-derived secretomes and exosomes, including engineered and primed variants, and to discuss translational barriers and safety considerations. A structured literature search was conducted using PubMed and Embase. Studies on molecular content, preclinical and clinical data, engineered EVs, oncologic safety, and regulatory aspects of MSC-derived products in dermatology were included. The MSC secretome includes cytokines, chemokines, growth factors, lipids, and regulatory RNAs that modulate inflammation, promote repair, and support skin homeostasis. Exosomes-particularly those from primed or engineered MSCs-play a key role via targeted microRNA delivery. Preclinical data support efficacy in atopic dermatitis, psoriasis, alopecia areata, vitiligo, chronic ulcers, and photoaging. Pilot clinical trials show promising safety and feasibility for topical or intradermal use. However, product heterogeneity, unclear dosing, long-term oncologic safety, and regulatory challenges persist. MSC-derived secretome and exosomes-especially those from primed or engineered MSCs-offer a promising acellular platform for dermatologic therapy. Clinical translation requires standardization, mechanistic validation, and rigorous safety evaluation through well-designed trials.