## 7 Preclinical Studies
### In Vivo Studies
in a recent study reported that hUCMSCs-Exo could inhibit psoriasis-like skin inflammation by suppressing the expression of IL-17, IL-23, and CCL20, thereby inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3) [131]. [PERSON] et al. in a mouse model of psoriasis demonstrated that local adipose-derived stromal cells' (ASCs') application inhibited the IMQ-induced upregulation of IL-17A and TNF-\(\alpha\) expression and maintained a clinically normal environment in murine skin [139]. An interesting study was conducted [PERSON], et al., in which they studied MSC-Exo with high PD-L1 expression (MSC-Exo-PD-L1) for the treatment of psoriasis in a mouse model of IMQ-induced psoriasis. MSC-Exo-PD-L1 significantly suppressed the inflammatory response via a reduction in immune cell infiltration, alteration of their phenotype, activation of immunoregulatory, cells and regulation of inflammatory and immunoregulatory cytokines in skin and the peripheral circulation, which was broken by PD-L1 antibody treatment. They showed that MSC-Exo-PD-L1 restored tissue lesions by inhibiting inflammatory immune cells via the PD-1/PD-L1 pathway [140]. [PERSON] et al. discovered that subcutaneous administration of hUC-MSCs drastically diminished the severity of IMQ-induced psoriasis-like dermatitis and suppressed the inflammatory cell response. Furthermore, they revealed that hUC-MSCs may repress skin inflammation, probably by inhibiting interleukin-17-producing \(\gamma\delta\) T cells [86]. In a recent study, [PERSON] et al. investigated the matrix metalloproteinase-13 (MMP13) that plays a key role in extracellular matrix (ECM) remodeling. They found that MMP13 was upregulated in the skin lesions of an IMQ-induced mouse model, and it was downregulated after intravenous infusion of hUC-MSCs. The researchers suggested that systematically infused hUC-MSCs exert a therapeutic effect on psoriasis through the TNF-\(\alpha\)/NF-\(\kappa\)B/MMP13 pathway [141]. In another recent study, [PERSON] et al. compared the efficacy of an infusion of AD-MSCs with the application of BM-MSCs in a mouse model of IMQ-induced psoriasis-like skin inflammation. They described that improved recovery of the skin was associated with increased IL-17A and TGF-\(\beta\) in the skin of mice treated with BM- or AD-MSCs, and they hypothesized that TGF-\(\beta\) promoted the controlled differentiation of keratinocytes, resulting in the decreased severity of psoriasis [142]. [PERSON] et al. reported that administration of UCB-MNC-Exo increases the number of Tregs in the skin and prevents acanthosis in imiquimod-induced psoriasis without affecting the overall disease burden [132]. Another group of researchers, [PERSON] et al., investigated the possible effect of hUC-MSCs when compared with conventional betamethasone cream treatment on IMQ-induced psoriasis-like skin lesion in a rat model. In their study, MSCs demonstrated efficacy in reducing disease severity. psoriatic symptoms, high expression of inflammatory mediators, and immune cell infiltration into the skin were alleviated after MSC administration. According to the research team, the mechanisms of action of MSCs are the regulation of immune cell infiltration, especially Th17 cells, and the regulation of epidermal functions and differentiation [143]. Thus, it can generally be said that a sufficiently large array of data on the application and the possible anti- and immunomodulatory effects of MSCs and MSC-Exo in psoriasis are being studied. The existing research data differ from each other due to various specific variables employed in data collection. These include the origin of MSCs (human or mouse), tissue source, route of administration, timing of treatment, number of repetitions, dosage, and mouse strains, which are all critical and have different effects on the therapeutic outcome.