Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
Cell Tissue Res. 2022 Jun;388(3):549-563. doi: 10.1007/s00441-022-03616-x. Epub 2022 Mar 26.
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.
间充质干细胞(MSCs)因其免疫调节能力在治疗自身免疫性疾病方面显示出巨大潜力,这在动物实验和临床试验中都得到了验证。银屑病是一种慢性、复发性的免疫相关性疾病。有限的研究表明,MSCs 可能是治疗银屑病的有效方法,但其潜在机制仍需阐明。在本研究中,我们将人脐带间充质干细胞(hUC-MSCs)皮下注射到咪喹莫特(IMQ)诱导的银屑病样皮肤炎症小鼠中,以探索这种细胞治疗的可行性。通过累积银屑病面积和严重程度指数评分和皮肤组织切片的表皮厚度来评估银屑病样皮炎的严重程度。流式细胞术分析用于检测皮肤引流淋巴结中的辅助性 T 细胞、调节性 T 细胞和γδ T 细胞。实时定量聚合酶链反应和酶联免疫吸附试验用于评估小鼠背部皮肤病变中银屑病相关细胞因子和趋化因子的表达水平。我们发现 hUC-MSCs 可显著减轻 IMQ 诱导的银屑病样皮炎的严重程度,并抑制炎症细胞反应。尽管 hUC-MSCs 的尾静脉注射也有效,但由于肺栓塞,其死亡率较高。相比之下,注射两百万个 hUC-MSCs 被确定为最佳治疗策略。此外,我们发现 hUC-MSCs 可能通过抑制白细胞介素-17 产生的γδ T 细胞来抑制皮肤炎症。总之,hUC-MSCs 的皮下给药可能是治疗银屑病的一种有前途的方法。我们的研究结果为 hUC-MSC 治疗银屑病的潜在机制提供了新的见解。