Efficacy and dose response of adipose-derived stem cells in ameliorating psoriasis-like inflammation in a mouse model

BACKGROUND: Mesenchymal stem cells (MSCs) derived from adipose tissue represent a type of MSCs that can be abundantly harvested from adult individuals, displaying high proliferative potential. Numerous studies have explored the application of adipose-derived stem cells (ADSCs) in immune-related disorders due to their immunomodulatory properties. Our research aims to evaluate the therapeutic potential of ADSCs in improving psoriasis-like lesions in a mouse model. METHODS: The study involved six groups of 6- to 8-week-old Balb/c mice, with 15 mice in each group: Group 1 (normal mice), Group 2 (Non- treated), Group 3 (Sham), Group 4 (positive control, topical corticosteroid therapy), Group 5 (treatment with low-dose of ADSCs subcutaneous injection, 106 6 ADSCs), Group 6 (treatment with high-dose of ADSCs subcutaneous injection, 2.5x106 6 ADSCs). Psoriasis-like lesions were induced through the continuous application of Imiquimod (IMQ) 5% cream for 6 days. Treatments were administered on day 3 when characteristic psoriatic lesions manifested. The modified Psoriasis Severity and Activity Index (PASI) for mice, histopathological features, and the expression levels of key disease-associated cytokines IL-17A and IL-23 in the psoriatic lesions were assessed on days 6 and 12. RESULTS: The ADSC-treated groups (Group 5 and 6) exhibited significantly lower severity of psoriasis-like lesions compared to the non- treated and sham groups. In terms of histological analysis, characteristic features of psoriasis, including parakeratosis, hyperkeratosis, acanthosis with elongation of the rete ridges, dilated blood vessels, and dermal inflammatory cell infiltration, were less pronounced in the ADSC-treated mice compared to non-treated and sham controls. Epidermal thickness was statistically reduced in the ADSC-treated groups (P<0.05). The expression of IL-17 and IL-23 in the psoriatic lesions also decreased after ADSC subcutaneous injection (P<0.05). Particularly, treatment efficacy increased with a high-dose of ADSCs compared to low-dose of ADSCs (P<0.05). CONCLUSIONS: ADSC subcutaneous injection demonstrates therapeutic potential in mitigating psoriasis-like skin lesions in the mouse model, avoiding the undesirable effects of topical steroids. Primary effects showed that the treatment efficacy depends on the dose of used ADSCs.