Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4⁺ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4⁺ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4⁺ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957

银屑病是一种常见的慢性免疫介导的全身性疾病，没有有效和持久的治疗方法。间充质干细胞 (MSC) 具有免疫调节特性。因此，我们进行了一项1/2a期单臂临床试验，以评估人脐带源性间充质干细胞（UMSCs）治疗银屑病的安全性和有效性，并初步探索可能的机制。17 名银屑病患者入组并接受了 UMSC 输注。分析了不良事件、实验室参数、PASI 和 PGA。我们在治疗和 6 个月的随访期间没有观察到明显的副作用。共有 47.1% (8/17) 的银屑病患者的 PASI 评分至少改善了 40%，而 17.6% (3/17) 的患者根据 PGA 评分没有疾病迹象或轻微疾病。男性的效率为 25%（2/8），女性的效率为 66.7%（6/9）。UMSC 移植 (UMSCT) 后，Tregs 和 CD4 的频率⁺记忆 T 细胞显着增加，T 辅助细胞 (Th) 17 和 CD4 ⁺幼稚 T 细胞在银屑病患者外周血 (PB) 中的频率显着降低。并且所有反应者在 UMSCT 后均显示 Tregs 和 CD4 ⁺记忆 T 细胞显着增加，Th17 细胞和血清 IL-17 水平显着降低。反应者中 Tregs 的基线水平明显低于无反应者。总之，异基因 UMSCT 对银屑病患者安全且部分有效，Tregs 水平可作为预测 UMSCT 临床疗效的有效生物标志物。试验注册临床试验 NCT03765957