2023年4月27日出版的《自然—细胞生物学》杂志发表了美国威尔康奈尔医学院Qiao Zhou研究组的最新研究成果。他们发现人胃源性胰岛素分泌类器官可恢复葡萄糖稳态。

研究人员揭示了一种利用人胃干细胞分化为胰岛样类器官的方法，该类器官含有胃胰岛素分泌（GINS）细胞，其分子特征和功能类似于β细胞。诱导因子NGN3和PDX1-MAFA的顺序激活诱导人胃干细胞进入独特的分化途径，包括SOX4^High内分泌和Galanin^High GINS前体，其具有β细胞特征，诱导效率接近70。在培养10天后GINS类器官在受到葡萄糖刺激后可分泌胰岛素，并在移植后可恢复糖尿病小鼠的葡萄糖稳态超过100天，这为利用该方法治疗糖尿病提供了依据。

据悉，肠道干细胞可通过活检获得，并在培养基中稳定增殖，为自体细胞疗法提供了宝贵的细胞资源。研究人员可以在小鼠肠道中诱导产生胰岛素的细胞，但还不能从人类肠道组织中获得丰富和持久的胰岛素分泌细胞来评估它们作为糖尿病细胞疗法的潜力。

附：英文原文

Title: Stomach-derived human insulin-secreting organoids restore glucose homeostasis

Author: Huang, Xiaofeng, Gu, Wei, Zhang, Jiaoyue, Lan, Ying, Colarusso, Jonathan L., Li, Sanlan, Pertl, Christoph, Lu, Jiaqi, Kim, Hyunkee, Zhu, Jian, Breault, David T., Svigny, Jean, Zhou, Qiao

Issue&Volume: 2023-04-27

Abstract: Gut stem cells are accessible by biopsy and propagate robustly in culture, offering an invaluable resource for autologous cell therapies. Insulin-producing cells can be induced in mouse gut, but it has not been possible to generate abundant and durable insulin-secreting cells from human gut tissues to evaluate their potential as a cell therapy for diabetes. Here we describe a protocol to differentiate cultured human gastric stem cells into pancreatic islet-like organoids containing gastric insulin-secreting (GINS) cells that resemble β-cells in molecular hallmarks and function. Sequential activation of the inducing factors NGN3 and PDX1-MAFA led human gastric stem cells onto a distinctive differentiation path, including a SOX4High endocrine and GalaninHigh GINS precursor, before adopting β-cell identity, at efficiencies close to 70%. GINS organoids acquired glucose-stimulated insulin secretion in 10days and restored glucose homeostasis for over 100days in diabetic mice after transplantation, providing proof of concept for a promising approach to treat diabetes.

DOI: 10.1038/s41556-023-01130-y

Source: https://www.nature.com/articles/s41556-023-01130-y