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, PD1^high 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.

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，PD1^高T 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。