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芬兰赫尔辛基大学Timo Otonkoski小组揭示干细胞来源的人类胰岛的功能、代谢和转录成熟。该研究于2022年3月3日在线发表于国际一流学术期刊《自然—生物技术》。

研究人员使用一个优化的方案产生了功能成熟的干细胞衍生胰岛（SC-islets），并将其与原生成人胰岛进行了全面的比较。在体外成熟过程中出现了双相葡萄糖刺激的胰岛素分泌，与细胞结构的重组和α细胞的增加有关。SC-islets的电生理学、信号传导和细胞外分泌与成年胰岛相似。尽管在糖酵解和线粒体葡萄糖代谢方面存在差异，但还是实现了葡萄糖反应性的胰岛素分泌。

在体外和整个6个月的小鼠体内移植过程中，SC-islets的单细胞转录组学显示了连续的成熟轨迹，最终形成了与原始胰岛密切相关的转录图谱。研究人员对SC-islets成熟的彻底评估突出了其先进的功能程度，并支持其用于进一步了解和防治糖尿病。

据悉，移植来自人类多能干细胞的胰岛细胞是一种有希望的糖尿病治疗方法。尽管在生成SC-islets方面取得了进展，但尚未对其功能特性进行详细描述。

附：英文原文

Title: Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells

Author: Balboa, Diego, Barsby, Tom, Lithovius, Vin, Saarimki-Vire, Jonna, Omar-Hmeadi, Muhmmad, Dyachok, Oleg, Montaser, Hossam, Lund, Per-Eric, Yang, Mingyu, Ibrahim, Hazem, Ntnen, Anna, Chandra, Vikash, Vihinen, Helena, Jokitalo, Eija, Kvist, Jouni, Ustinov, Jarkko, Nieminen, Anni I., Kuuluvainen, Emilia, Hietakangas, Ville, Katajisto, Pekka, Lau, Joey, Carlsson, Per-Ola, Barg, Sebastian, Tengholm, Anders, Otonkoski, Timo

Issue&Volume: 2022-03-03

Abstract: Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.

DOI: 10.1038/s41587-022-01219-z

Source: https://www.nature.com/articles/s41587-022-01219-z

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
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