Exosome‐Based Therapy: A Comparative Study of Adipose‐ and Umbilical Cord‐Derived Mesenchymal Stem Cells‐Derived Exosomes in Psoriatic Mouse Model

ABSTRACT Exosomes are nanosized extracellular vesicles that mediate intercellular communication by transferring bioactive molecules. Mesenchymal stem cells (MSCs) from different tissue sources secrete exosomes with potentially distinct therapeutic properties. In this study, we compared the anti‐inflammatory efficacy of exosomes derived from human adipose‐derived MSCs (hADMSCs‐EXOs) and human umbilical cord‐derived MSCs (hUCMSCs‐EXOs), together with desoximetasone (DSM), in an imiquimod‐induced psoriasis mouse model. Psoriasiform lesions were induced, and treatment outcomes were assessed through clinical, histological, and immunological assessments. Both hADMSCs‐EXOs and hUCMSCs‐EXOs significantly attenuated psoriasiform lesions, as clinically evidenced by reduced cumulative Psoriasis Severity Index (PSI) scores by day 6 of treatment. Notably, hUCMSCs‐EXOs and DSM significantly reduced epidermal and dermal thickness to no significant difference compared to the control group. Immune cell infiltration, including CD3 + , CD4 + , CD8 + T cells, CD68 + macrophages, CD117 + mast cells, and neutrophils, was also markedly reduced in the hUCMSCs‐EXOs and DSM groups. Importantly, unlike DSM, hUCMSCs‐EXOs did not induce skin thinning or systemic adverse effects. Growth factor (GF) profiling revealed that hADMSCs‐EXOs were enriched in FGFs, PDGFs, and VEGF, whereas hUCMSCs‐EXOs contained higher levels of HGF, a key modulator of immunoregulation and tissue repair. Collectively, these findings suggest that MSC‐derived exosomes exert therapeutic effects through both anti‐inflammatory and regenerative mechanisms, with hUCMSCs‐EXOs demonstrating superior anti‐inflammatory efficacy over hADMSCs‐EXOs and a lower likelihood of inducing local or systemic adverse effects compared with DSM. Given the influence of MSC tissue origin on exosome content and function, our results support the potential of hUCMSCs‐EXOs as a promising steroid‐sparing therapeutic approach for psoriasis.