Abstract

Abstract: Psoriasis is a chronic immune-mediated skin disorder driven by dysregulation of the IL-23/IL-17 axis. Human umbilical cord–derived mesenchymal stem cells (hUC-MSCs) possess immunomodulatory and anti-inflammatory properties, making them a potential therapeutic candidate for psoriasis treatment. In this study, we evaluated the therapeutic effects of localized subcutaneous administration of hUC-MSCs in an imiquimod (IMQ)-induced psoriasis-like mouse model.

Methods: BALB/c mice received daily topical IMQ for six consecutive days. A single dose of hUC-MSCs (2.5 × 10⁶ cells) was administered subcutaneously at lesional sites on day 2. Treatment with hUC-MSCs significantly attenuated clinical severity, as evidenced by reduced erythema, scaling, and skin thickness, along with decreased epidermal hyperplasia and inflammatory infiltration. 

Results: Analysis demonstrated a reduction in IL-17A and IL-23 expression in lesional skin at day 6 following hUC-MSC treatment. Consistently, quantitative PCR revealed downregulation of multiple psoriasis-associated inflammatory genes, with more pronounced suppression observed for downstream mediators such as Tnf and Ccl20, while upstream cytokines within the IL-23/IL-17 axis (Il17a, Il23) showed more moderate changes. By day 12, gene expression levels declined across all groups, reflecting the self-resolving nature of the IMQ-induced model.

Conclusion: Overall, these findings demonstrate that localized subcutaneous administration of hUC-MSCs attenuates psoriasis-like inflammation and accelerates lesion resolution in an IMQ-induced mouse model, potentially through modulation of key proinflammatory cytokines. Further studies are required to evaluate long-term efficacy and to elucidate the underlying mechanisms of action.