Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases due to their immunomodulatory capability, which has been verified in both animal experiments and clinical trials. Psoriasis is a chronic and remitting immune-related disease. Limited studies have demonstrated that MSCs might be an effective therapeutic approach for managing psoriasis, whose underlying mechanism remains to be elucidated. In our present study, human umbilical cord-derived MSCs (hUC-MSCs) were subcutaneously injected into mice with imiquimod (IMQ)-induced psoriasis-like skin inflammation to explore the feasibility of this cellular therapy. The severity of psoriasis-like dermatitis was evaluated by cumulative psoriasis area and severity index score and epidermal thickness of skin tissue sections. Flow cytometric analysis was utilized to detect T helper cells, regulatory T cells, and γδ T cells in skin-draining lymph nodes. Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the expression levels of psoriasis-related cytokines and chemokines in mouse dorsal skin lesions. We discovered that hUC-MSCs drastically diminished the severity of IMQ-induced psoriasis-like dermatitis and suppressed inflammatory cell response. Although the tail vein injection of hUC-MSCs was also effective, it was correlated with higher mortality owing to pulmonary embolism. By comparison, subcutaneous injection with two million hUC-MSCs was identified to be the optimal therapeutic strategy. Furthermore, we uncovered that hUC-MSCs might repress skin inflammation probably through inhibiting interleukin-17-producing γδ T cells. In conclusion, subcutaneous administration of hUC-MSCs might be a promising therapeutic approach for psoriasis. Our findings provide novel insights into the underpinning mechanism of hUC-MSC treatment in the management of psoriasis.
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The datasets used during the current study are available from the corresponding author on reasonable request.
Mesenchymal stem cells
Human umbilical cord-derived MSCs
Standard operating procedure
Tumor necrosis factor
Psoriasis area severity index
Transforming growth factor
T helper 17
Hematoxylin and eosin
Systemic lupus erythematosus
Extracellular matrix protein 1
Melanoma cell adhesion molecule
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This work was sponsored by grants from National Natural Science Foundation of China (No. 81872522, 82073429, 81903205, 81803120, and 81900612), the National Key Research and Development Program of China (No. 2018YFC1705301, 2018YFC1705305), Innovation Program of Shanghai Municipal Education Commission (No. 2019–01-07–00-07-E00046), the Program of Science and Technology Commission of Shanghai Municipality (No. 18140901800), Excellent Subject Leader Program of Shanghai Municipal Commission of Health and Family Planning (No. 2018BR30), Clinical Research Program of Shanghai Hospital Development Center (No. SHDC2020CR1014B, SHDC12018X06), Shanghai Sailing Program (No. 19YF1438100), Program of Shanghai Academic Research Leader (No. 20XD1403300), the Fundamental Research Funds for the Central Universities (#22120210566), and Research Program of Shanghai Skin Disease Hospital (No. 2019KYQD08).
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Supplementary file1 Fig. S1 Schematic of the experimental procedures. a Experimental design of Fig. 2. b Experimental design of Fig. 3. c Experimental design of Fig. 4. d Experimental design of Fig. 5 (TIF 284 KB)
Supplementary file2 Fig. S2 The number of injection points, time points of administration, or injection volumes do not influence the therapeutic effects of hUC-MSCs. a Disease model mice were subcutaneously injected with two million hUC-MSCs on day 0 at one injection point in 500 μl PBS (group A), at five injection points in 500 μl PBS (group B), at one injection point in 200 μl PBS (group C); group D was only given 200 μl PBS at one injection point. The experimental mice were sacrificed after six consecutive days of IMQ application (n = 54, three independent experiments, three mice for each group, and 18 mice for each experiment). b Representative pictures of mouse skin lesions. c Evaluation of PASI score. d H&E staining and calculated epidermal thicknesses e. * indicates comparison with untreated psoriatic group and unpaired t test was used for statistical analysis. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 (TIF 986 KB)
Supplementary file3 Fig. S3 hUC-MSC treatment modulates the expression of inflammatory cytokines and chemokines. Mice were treated as in Fig. 5. Dorsal skin samples from control mice, disease model mice, and hUC-MSC-treated IMQ mice were collected, and IL-4, IL-10, IL-6, IL-17, IL-22, IL-23A, IL-1β, TNF-α, IFN-γ, TGF-β, and CXCL-15 mRNA expression was analyzed by quantitative RT-qPCR (n = 48, four independent experiments, three mice for each group and 12 mice for each experiment). The data are the mean ± SEM, and unpaired t test was used for statistical analysis. * indicates comparison with untreated psoriatic group and unpaired t test was used for statistical analysis. *P < 0.05. (TIF 441 KB)
Supplementary file4 Fig. S4 hUC-MSCs do not alter IL-6 and TNF-α protein production. Mice were treated as in Fig. 5. Dorsal skin samples from control mice, disease model mice, and hUC-MSC-treated IMQ mice were collected, and protein levels of IL-6 a and TNF-α b were evaluated quantitatively by ELISA (n = 48, four independent experiments, three mice for each group, and 12 mice for each experiment). The data are the mean ± SEM, and unpaired t test was used for statistical analysis. * indicates comparison with untreated psoriatic group and unpaired t test was used for statistical analysis. *P < 0.05. (TIF 84 KB)
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Chen, Y., Hu, Y., Zhou, X. et al. Human umbilical cord-derived mesenchymal stem cells ameliorate psoriasis-like dermatitis by suppressing IL-17-producing γδ T cells. Cell Tissue Res 388, 549–563 (2022). https://doi.org/10.1007/s00441-022-03616-x