背景：1型糖尿病（T1D）是一种T细胞介导的自身免疫性疾病，可导致胰岛β细胞缺乏。在T1D中克服自身免疫的复杂性导致了研究界在用常规免疫疗法设计成功治疗时面临的挑战。克服自身免疫T细胞记忆是关键障碍之一。
方法：在此开放标签中，第一阶段/第二阶段研究，高加索T1D患者（N=15）接受了干细胞教育者（SCE）治疗的两种治疗，一种使用人多能脐带血来源的多能干细胞（CB-SC）的方法。SCE治疗涉及闭环系统，该系统在体外用CB-SCs短暂治疗患者的淋巴细胞，并将“受过教育的”淋巴细胞（但不包括CB-SCs）返回患者的血液循环。这项研究在ClinicalTrials.gov注册，NCT01350219。
结果：临床数据表明SCE治疗在所有受试者中均具有良好的耐受性。初始CD4(+)T细胞的百分比在26周时显著增加,并且在56周的最后随访中保持。CD4（）中枢记忆T细胞（TCM）的百分比在18周时显着并不断增加。CD4(+)效应记忆T细胞(TEM)和CD8(+)TEM细胞分别在18周和26周显著降低。其他临床数据表明C-C趋化因子受体7（CCR7）表达对幼稚T的调节，TCM,和TEM细胞。经过两次SCE治疗，胰岛β细胞功能得到改善，并在有残余β细胞功能的个体中得到维持，但不是在那些没有残余β细胞功能。
结论：目前的临床数据证明了SCE治疗在免疫调节中的安全性和有效性。SCE治疗提供了自身免疫记忆的持久逆转，可以改善白种人受试者的胰岛β细胞功能。
背景：ObraSocial\“LaCaixa\”，塞卢德·卡洛斯三世研究所，ReddeInvestigaciónRenal,欧盟联邦基金,PrincipadodeAsturias,FICYT,哈肯萨克大学医学中心基金会.
BACKGROUND: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet β cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles.
METHODS: In this open-label, phase 1/phase 2
study, Caucasian T1D patients (N = 15) received two treatments with the Stem Cell Educator (SCE) therapy, an approach that uses human multipotent cord blood-derived multipotent stem cells (CB-SCs). SCE therapy involves a closed-loop system that briefly treats the patient\'s lymphocytes with CB-SCs in vitro and returns the \"educated\" lymphocytes (but not the CB-SCs) into the patient\'s blood circulation. This
study is registered with ClinicalTrials.gov, NCT01350219.
RESULTS: Clinical data demonstrated that SCE therapy was well tolerated in all subjects. The percentage of naïve CD4(+) T cells was significantly increased at 26 weeks and maintained through the final follow-up at 56 weeks. The percentage of CD4(+) central memory T cells (TCM) was markedly and constantly increased at 18 weeks. Both CD4(+) effector memory T cells (TEM) and CD8(+) TEM cells were considerably decreased at 18 weeks and 26 weeks respectively. Additional clinical data demonstrated the modulation of C-C chemokine receptor 7 (CCR7) expressions on naïve T, TCM, and TEM cells. Following two treatments with SCE therapy, islet β-cell function was improved and maintained in individuals with residual β-cell function, but not in those without residual β-cell function.
CONCLUSIONS: Current clinical data demonstrated the safety and efficacy of SCE therapy in immune modulation. SCE therapy provides lasting reversal of autoimmune memory that could improve islet β-cell function in Caucasian subjects.
BACKGROUND: Obra Social \"La Caixa\", Instituto de Salud Carlos III, Red de Investigación Renal, European Union FEDER Funds, Principado de Asturias, FICYT, and Hackensack University Medical Center Foundation.
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