Amelioration of psoriasis-like skin lesions by human amniotic mesenchymal stem cells: insights from multiomics profiling in mice

Background Psoriasis is a multifactorial, chronic inflammatory skin disease. Current treatment modalities are limited by suboptimal patient responses and high recurrence rates after discontinuation. Consequently, there is an urgent need to develop novel therapeutic strategies for psoriasis. Methods An imiquimod‐induced mouse model of psoriasis was established, and human amniotic mesenchymal stem cell (hAMSC) were subsequently administered to evaluate their therapeutic efficacy. Bioinformatic analyses of Gene Expression Omnibus (GEO) datasets GSE39035 and GSE97311 were performed to identify potential hAMSC therapeutic target genes. Using data from GSE228421, a single-cell transcriptomic atlas of psoriasis was constructed to examine the distribution and functional roles of these target genes across different cell populations. Results By integrating an imiquimod-induced murine model with comprehensive bioinformatic analyses of GEO datasets, we demonstrated that hAMSC administration significantly ameliorated psoriasis-like skin lesions, restored epidermal architecture, and reduced PASI and Baker scores. This therapeutic efficacy was accompanied by the alleviation of splenomegaly and a systemic reduction in inflammatory cytokines (IL-17 and TNF-α) without inducing hepatotoxicity. In vitro experiments further confirmed that hAMSCs inhibited TNF-α-induced keratinocyte proliferation and reactive oxygen species (ROS) generation. Transcriptomic profiling identified key immune-related targets, revealing that hAMSCs significantly modulated the expression of genes such as MMP9, S100A9, and BACH2. It is worth noting that single-cell atlas analysis has revealed that S100A9 and MMP9 play significant roles respectively in psoriasis-related CD8-IL17A T cells and M2-like macrophages, and further clarified the functional characteristics of S100A9 in the temporal development process of psoriasis fibroblasts and keratinocytes. Conclusions In summary, our findings confirm the efficacy and safety of hAMSCs in the treatment of psoriasis and elucidate the underlying mechanisms of their therapeutic action.