Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 W, Polk Street, Chicago, IL 60612, USA.
BMC Med. 2013 Jul 9;11:160. doi: 10.1186/1741-7015-11-160.
BACKGROUND: The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease. METHODS: In an open-label, phase 1/phase 2 study, patients (N=36) with long-standing T2D were divided into three groups (Group A, oral medications, n=18; Group B, oral medications+insulin injections, n=11; Group C having impaired β-cell function with oral medications+insulin injections, n=7). All patients received one treatment with the Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent cord blood-derived multipotent stem cells (CB-SCs), and returns the educated autologous cells to the patient's circulation. RESULTS: Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median glycated hemoglobin (HbA1C) in Group A and B was significantly reduced from 8.61%±1.12 at baseline to 7.25%±0.58 at 12 weeks (P=2.62E-06), and 7.33%±1.02 at one year post-treatment (P=0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post-treatment. Notably, the islet beta-cell function in Group C subjects was markedly recovered, as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production. CONCLUSIONS: Clinical data from the current phase 1/phase 2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in metabolic control for individuals with moderate or severe T2D who receive a single treatment. In addition, this approach does not appear to have the safety and ethical concerns associated with conventional stem cell-based approaches. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01415726.
背景：2 型糖尿病（T2D）的患病率在全球范围内不断上升，给卫生系统带来了巨大负担，这凸显出需要开发创新的治疗方法来克服免疫功能障碍，而免疫功能障碍可能是 T2D 患者发生胰岛素抵抗的关键因素。这表明免疫调节可能是治疗这种疾病的有用工具。
方法：在一项开放标签的 1 期/2 期研究中，将长期患有 T2D 的患者（N=36）分为三组（A 组，口服药物，n=18；B 组，口服药物+胰岛素注射，n=11；C 组，口服药物+胰岛素注射治疗β细胞功能受损，n=7）。所有患者均接受了一次 Stem Cell Educator 治疗，该治疗方法是将患者的血液通过闭环系统循环，将单核细胞与全血分离，短暂地与贴壁的脐带血来源的多能干细胞（CB-SCs）共培养，然后将经过教育的自体细胞回输到患者的循环中。
结果：临床发现，接受 Stem Cell Educator 治疗后，T2D 患者的代谢控制得到改善，炎症标志物减少。A 组和 B 组的中位糖化血红蛋白（HbA1C）水平从基线时的 8.61%±1.12 显著降低至 12 周时的 7.25%±0.58（P=2.62E-06）和治疗后 1 年时的 7.33%±1.02（P=0.0002）。胰岛素抵抗的稳态模型评估（HOMA）（HOMA-IR）显示，治疗后胰岛素敏感性得到改善。值得注意的是，C 组患者的胰岛β细胞功能明显恢复，表现为 C 肽水平的恢复。机制研究表明，Stem Cell Educator 治疗通过对单核细胞的免疫调节和平衡 Th1/Th2/Th3 细胞因子的产生来逆转免疫功能障碍。
结论：目前的 1 期/2 期研究的临床数据表明，Stem Cell Educator 治疗是一种安全的方法，可使接受单次治疗的中重度 T2D 个体的代谢控制得到持久改善。此外，该方法似乎没有与传统基于干细胞的方法相关的安全性和伦理问题。
临床试验注册：ClinicalTrials.gov 编号，NCT01415726。
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