Section of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 West Polk Street, Chicago, IL 60612, USA.
BMC Med. 2012 Jan 10;10:3. doi: 10.1186/1741-7015-10-3.
BACKGROUND: Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem cells (CB-SCs) can control autoimmune responses by altering regulatory T cells (Tregs) and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. METHODS: We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n=15) with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41), and median diabetic history was 8 years (range: 1 to 21). RESULTS: Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C) values, and decrease the median daily dose of insulin in patients with some residual β cell function (n=6) and patients with no residual pancreatic islet β cell function (n=6). Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n=3) did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS), increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. CONCLUSIONS: Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of islet β cells. Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01350219.
背景：无法控制自身免疫是开发 1 型糖尿病（T1D）治愈方法的主要障碍。有证据表明，人脐带血来源的多能干细胞（CB-SCs）可以通过改变调节性 T 细胞（Tregs）和人胰岛β细胞特异性 T 细胞克隆来控制自身免疫反应，这为克服 T1D 潜在的自身免疫提供了一种新方法。
方法：我们开发了一种干细胞教育者疗法程序，其中患者的血液在闭环系统中循环，该系统将淋巴细胞与全血分离，并在将其返回患者循环之前与贴壁 CB-SCs 短暂共培养。在一项开放标签的 1/2 期研究中，15 名 T1D 患者接受了一次干细胞教育者治疗。中位年龄为 29 岁（范围：15 至 41 岁），中位糖尿病病史为 8 年（范围：1 至 21 年）。
结果：所有参与者均耐受良好，仅通过两次静脉穿刺引起轻微疼痛，无不良事件。干细胞教育者疗法可显著改善 C 肽水平，降低糖化血红蛋白 A1C（HbA1C）中位数，减少有一定残留β细胞功能（n=6）和无残留胰岛β细胞功能（n=6）的患者的每日胰岛素剂量中位数。治疗还通过 40 周增加了基础和葡萄糖刺激的 C 肽水平。然而，对照组（n=3）的参与者在任何随访中均未显示出显著变化。接受干细胞教育者治疗的个体表现出共刺激分子（特别是 CD28 和 ICOS）表达增加，CD4+CD25+Foxp3+Tregs 数量增加以及 Th1/Th2/Th3 细胞因子平衡恢复。
结论：干细胞教育者疗法是安全的，在中度或重度 T1D 患者中，单次治疗可持久改善代谢控制。初步结果表明，干细胞教育者疗法可逆转自身免疫并促进胰岛β细胞的再生。CB-SC 成功的免疫调节以及由此导致的患者病情改善可能对其他自身免疫和炎症相关疾病具有重要意义，而没有与传统基于干细胞的方法相关的安全性和伦理问题。
试验注册：ClinicalTrials.gov 编号，NCT01350219。
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