## 7 Preclinical Studies  
### In Vitro Studies  
In vitro studies investigating the effects of MSCs on psoriasis offer intricate insights into the pathophysiology of this complex dermatological disorder. In the context of psoriasis, the microenvironment exhibits distinct characteristics compared to atopic dermatitis and healthy skin. This specific environment induces resident MSCs to release proinflammatory and angiogenic mediators, while simultaneously diminishing their antioxidant capacity, a combination that contributes to the development of psoriatic skin lesions. This highlights the importance of understanding the dynamic interplay between the microenvironment and resident MSC populations in disease progression [123]. Furthermore, psoriatic dermal MSCs (p-DMSCs) play a multifaceted role in the pathogenesis of psoriasis. These cells display a remarkable ability to upregulate the expression of vascular endothelial growth factor (VEGF), thereby promoting angiogenesis and facilitating the migration of human umbilical vein endothelial cells (HUVECs). This angiogenic potential suggests a contributory role of p-DMSCs in the enhanced vascularity observed in psoriatic lesions [124]. Additionally, p-DMSCs exhibit a dual effect on keratinocytes, the predominant cell type in the epidermis. They not only promote keratinocyte proliferation but also suppress apoptosis by downregulating caspase-3 expression. Consequently, this dysregulation in keratinocyte dynamics leads to hyperproliferation and impaired apoptosis, exacerbating the inflammatory response within the epidermal layer [125]. Moreover, normal dermal MSCs (n-DMSCs) have been shown to outperform p-DMSCs in suppressing T-cell proliferation and enhancing Treg activity. It was found that p-DMSCs have a higher expression of genes responsible for the activation of Th1 and Th17 cytokines than n-DMSCs. Compared to p-DMSCs, n-DMSCs not only more effectively inhibit CD3 T-cell proliferation but also promote T-cell apoptosis, leading to a reduction in the Th1/Treg ratio. This suggests that n-DMSCs could partially restore the immune balance through upregulation of TGF-\(\beta\) receptor signaling pathways, enhancing the immunosuppressive function of Tregs [126; 127]. Finally, a study aimed to evaluate the influence of hUC-MSCs on MSCs derived from psoriatic patients (PsO-MSCs), and it shed light on the interaction between different MSC populations. hUC-MSCs and PsO-MSCs were isolated and characterized, followed by an indirect co-culture experiment. The effects of co-culturing on the proliferation and expression of cytokines associated with Th1/Th17 and Th2 pathways were assessed. Intriguingly, the results revealed that prior to co-culturing, the proliferation of PsO-MSCs was significantly higher than that of hUC-MSCs, suggesting inherent differences in the proliferative capacities of MSCs derived from psoriaticatic patients compared to those from healthy sources [128]. Moreover, both unmodified MSCs and those treated with superoxide dismutase 3 (SOD3) exhibit profound inhibition of T-cell proliferative responses in vitro. This inhibition underscores the potential of MSC-based therapies in modulating the dysregulated immune responses characteristic of psoriasis, potentially offering a novel avenue for therapeutic intervention [129]. Furthermore, recent research highlights that exosomes derived from IFN-\(\gamma\)-stimulated hUC-MSCs exhibit notable immunomodulatory effects. These vesicles, by inhibiting peripheral blood mononuclear cell and T-cell proliferation, significantly reduced cytokine production linked to inflammation in vitro [130]. One compelling finding is the capacity of human umbilical cord MSC-derived exosomes (hUCMSCs-Exo) to suppress DCs' maturation and activation. This suppression is accompanied by a significant reduction in the expression levels of IL23, a pivotal cytokine implicated in the initiation and perpetuation of psoriatic inflammation [131].