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Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes
Cell Stem Cell ( IF 19.8 ) Pub Date : 2021-12-02 , DOI: 10.1016/j.stem.2021.10.003
Adam Ramzy 1 , David M Thompson 2 , Kirsten A Ward-Hartstonge 3 , Sabine Ivison 3 , Laura Cook 3 , Rosa V Garcia 3 , Jackson Loyal 2 , Peter T W Kim 4 , Garth L Warnock 4 , Megan K Levings 5 , Timothy J Kieffer 6
Affiliation  

An open-label, first-in-human phase 1/2 study is being conducted to evaluate the safety and efficacy of pancreatic endoderm cells (PECs) implanted in non-immunoprotective macroencapsulation devices for the treatment of type 1 diabetes. We report an analysis on 1 year of data from the first cohort of 15 patients from a single trial site that received subcutaneous implantation of cell products combined with an immunosuppressive regimen. Implants were well tolerated with no teratoma formation or severe graft-related adverse events. After implantation, patients had increased fasting C-peptide levels and increased glucose-responsive C-peptide levels and developed mixed meal-stimulated C-peptide secretion. There were immunosuppression-related transient increases in circulating regulatory T cells, PD1high T cells, and IL17A+CD4+ T cells. Explanted grafts contained cells with a mature β cell phenotype that were immunoreactive for insulin, islet amyloid polypeptide, and MAFA. These data, and associated findings (Shapiro et al., 2021), are the first reported evidence of meal-regulated insulin secretion by differentiated stem cells in patients.



中文翻译:

植入的多能干细胞来源的胰腺内胚层细胞在 1 型糖尿病患者中分泌葡萄糖反应性 C 肽

正在进行一项开放标签、首次人体 1/2 期研究,以评估植入非免疫保护性宏封装装置中的胰腺内胚层细胞 (PEC) 治疗 1 型糖尿病的安全性和有效性。我们报告了对来自单一试验地点的第一批 15 名患者的 1 年数据分析,这些患者接受了皮下植入细胞产品并结合免疫抑制方案。植入物耐受性良好,没有形成畸胎瘤或严重的移植相关不良事件。植入后,患者的空腹 C 肽水平和葡萄糖反应性 C 肽水平增加,并出现混合膳食刺激的 C 肽分泌。循环调节性 T 细胞存在免疫抑制相关的短暂增加,PD1T 细胞和 IL17A + CD4 + T 细胞。移植的移植物包含具有成熟 β 细胞表型的细胞,这些细胞对胰岛素、胰岛淀粉样蛋白多肽和 MAFA 具有免疫反应性。这些数据和相关发现(Shapiro 等人,2021 年)是第一个报道的患者分化干细胞通过膳食调节胰岛素分泌的证据。

更新日期:2021-12-02
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