# Novel Small-Molecule Treatment and Emerging Biological Therapy for Poriasis
## 4 Cell-Based Therapy  
### Mesenchymal Stem Cell  
Mesenchymal stem cell therapy (MSC therapy) is a cell-based approach for managing inflammatory diseases. MSCs possess strong immunosuppressive properties, inhibiting T cell maturation and altering the behavior of immune cells, as evidenced by extensive clinical data. The safety of MSCs remains controversial. In addition, the industrialization of homologous MSCs is high-cost, and there are problems with storage and aging during cell expansion. Therefore, the clinical application of MSCs is challenging, and pulmonary embolism is prone to form after intravenous administration. Compared with MSCs, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) not only share similar immunomodulatory capabilities but also offer benefits such as low immunogenicity and high plasticity [131]. The extracellular matrix (ECM) undergoes remodeling via matrix metalloproteinase-13 (MMP-13), a process vital for normal functions such as wound healing and angiogenesis. Disruption of this process is associated with the development of various inflammatory diseases. [PERSON] et al. noted a marked rise in MMP-13 expression in skin lesions of an IMQ-induced mouse model and found that TNF-\(\alpha\) boosts MMP-13 levels in keratinocytes via the NF-\(\kappa\)B signaling pathway. Following the co-culture of hUC-MSCs with THP-1 cells or PMA-induced THP-1 cells in vitro, TNF-\(\alpha\) levels in the supernatant dropped, while IL-10 levels rose significantly. IL-10, a crucial immunomododulatory cytokine, plays a pivotal role in suppressing inflammatory immune responses, mainly by inhibiting the activation of immune-related cells. When hUC-MSCs were intravenously administered to IMQ-induced mice, MMP-13 expression was notably reduced. In conclusion, hUC-MSC treatment can inhibit abnormal keratinocyte proliferation, cease the cell cycle at the G1 phase, and reduce the secretion of proinflammatory cytokines in monocytes and macrophages [132]. Bone marrow-derived MSCs are currently the most commonly used MSCs in clinical practice and are the gold standard of MSC therapy. The yield of MSCs derived from adipose tissue is 500-fold higher than that from bone marrow, which is expected to be a potential source of MSCs. [PERSON] et al. used highly physiological condition-matched mouse medulla osmium (MO) and fat tissue (FT)-derived MSCs to investigate the therapeutic effect on imiquimod-induced mouse models. Licensed MSCs mean that the anti-inflammatory function of the MSCs has been enhanced by IFN-\(\gamma\) treatment combined with TNF-\(\alpha\) and IL-1\(\beta\) prior to administration. Unlicensed MSCs mean no cytokine treatment before administration. Both unlicensed MO MSCs and FT MSCs reduced the total PASI score from 6.0 to 2.0. Unlicensed MO MSCs and FT MSCs upregulated the secretion of interleukin-6 while reducing epidermal thickness. The application of licensed MSCs decreased their ability to secrete IL-6; the results implied a reduction in their therapeutic potential. In conclusion, MSCs exert therapeutic effects by secreting cytokines themselves, thereby influencing the pathological process of psoriasis [133]. [PERSON] et al. injected IFN-\(\gamma\)- and TNF-\(\alpha\)-stimulated umbilical cord-derived MSCs subcutaneously into psoriasis lesions, and neutrophil infiltration was significantly reduced. They inferred that MSC-IT suppresses inflammation through the secretion of TSG-6. The results showed that the therapeutic effect of TSG-6 siRNA-transduced MSCs was lost. Moreover, their findings revealed that TSG-6 has the capacity to suppress the recruitment of neutrophils through the downregulation of CXCL1 expression. This mechanism is potentially linked to the decreased levels of STAT1 phosphorylation observed in keratinocytes [134]. [PERSON] et al. developed an optimized acellular method for extracting ECM from fish skin, which was then mixed with metal Ru and persulfate salt to produce a photoactivated ECM bioink.