Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies
Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies
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DOI：
10.1002/stem.2401
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发表时间：
2017-01-01
期刊：
影响因子：
5.2
通讯作者：
Kim, Tae-Yoon
中科院分区：
文献类型：
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作者：
Kim, Hyung-Sik;Lee, Ji Hyun;Kim, Tae-Yoon
在临床前研究中，间充质干细胞(MSCs)已被证明对特应性皮炎(AD)具有有效的治疗作用。然而，骨髓间充质干细胞治疗阿尔茨海默病的安全性和有效性尚未在临床研究中得到证实。为确定人脐血间充质干细胞(hUCB-MSCs)治疗AD的安全性和有效性，对34例中重度AD患者进行两期临床试验，分别随访1个月和3个月。患者被随机分配到低剂量(2.5×10(7))或大剂量(5.0×10(7))的hUCB-MSCs皮下注射。以湿疹面积和严重程度指数(EASI)评分、调查者总体评估(IGA)评分、特应性皮炎严重程度评分(SCORAD)评分、不良反应评估和血清生物标记物水平为终点。单独使用hUCB-MSCs可剂量依赖性地改善AD的临床表现。高剂量hUCB-MSC治疗组55%的患者EASI评分下降50%。高剂量组的IGA评分和SCORAD评分分别下降33%和50%。特别是，大剂量hUCB-MSCs组的瘙痒评分降低了58%。治疗后血清IgE水平及外周血嗜酸粒细胞数均明显下降。没有发生严重的不良事件，也没有患者因不良事件而终止试验。这是第一份证明细胞疗法显著改善AD特征的报告。这些数据表明，输注hUCB-MSCs可能是治疗中重度AD的一种有效方法。
Mesenchymal stem cells (MSCs) have been proven to be therapeutically effective against atopic dermatitis (AD) in preclinical studies. However, the safety and efficacy of MSCs against AD have not yet been investigated in a clinical study. To establish the safety and efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) in AD, 34 adult patients with moderate-to-severe AD were enrolled in two phase trials with a follow-up for 1 month and 3 months, respectively. Patients were randomly allocated to receive low dose (2.5 x 10(7)) or high dose (5.0 x 10(7)) of hUCB-MSCs subcutaneously. An Eczema Area and Severity Index (EASI) score, Investigator's Global Assessment (IGA) score, Severity Scoring for Atopic Dermatitis (SCORAD) score, adverse effect assessments, and serum biomarker levels were evaluated as end points. A single treatment of hUCB-MSCs resulted in dose-dependent improvements in AD manifestation. Fifty-five percent of patients in high dose hUCB-MSC-treated group showed a 50% reduction in the EASI score. The IGA score and SCORAD score decreased by 33% and 50%, respectively, in high dose-treated group. Particularly, the administration of high dose hUCB-MSCs reduced the pruritus score by 58%. The serum IgE levels and number of blood eosinophils were down-regulated by the treatment. No serious adverse events occurred, and none of the patients discontinued the trial due to adverse events. This is the first report to demonstrate a marked improvement of AD features with cell therapeutics. These data suggest that the infusion of hUCB-MSCs might be an effective therapy for patients with moderate-to-severe AD.