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Topical therapies and phototherapy are often inadequate, while systemic agents and biologics are limited by toxicity, high cost, and restricted reimbursement criteria, leaving patients with moderate disease without adequate therapeutic options. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising acellular therapeutic modality that harnesses the immunomodulatory and regenerative properties of parent MSCs. Unlike systemic biologics, MSC-EVs act locally and non-immunosuppressively. Topically applied MSC-EVs have demonstrated the ability to modulate cutaneous inflammation by attenuating complement activation [via CD59-mediated inhibition of complement terminal component 5b-9 (C5b-9) complex formation], reducing neutrophil infiltration, and subsequently lowering IL-17 and IL-23 expression in psoriatic lesions. Preclinical and early clinical studies suggest that MSC-EVs can restore local immune homeostasis through paracrine extracellular mechanisms, without systemic absorption or adverse effects. MSC-EVs represent a new class of cell-free nanotherapeutics inspired by biologics, capable of localized immunomodulation in psoriasis. By combining biologic-like efficacy with the safety and accessibility of topical therapy, MSC-EVs may bridge the long-standing therapeutic gap in moderate psoriasis. This review discusses current treatment limitations, the mechanistic rationale for MSC-EVs in psoriatic inflammation, and their potential to redefine dermatologic immunotherapy.<\/jats:p>","DOI":"10.20517\/evcna.2025.150","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:29:20Z","timestamp":1777008560000},"page":"580-94","update-policy":"https:\/\/doi.org\/10.20517\/oae.crossmark.policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as a novel topical immunomodulatory therapy for psoriasis: bridging the therapeutic gap in moderate disease"],"prefix":"10.20517","volume":"7","author":[{"given":"Thong Teck","family":"Tan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kok Hian","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai 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