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通过共培养内胚层和中胚层祖细胞从诱导多能干细胞快速生成肺类器官用于肺病建模

Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling.

作者信息

Mitchell Adam, Yu Chaowen, Zhao Xiangjun, Pearmain Laurence, Shah Rajesh, Hanley Karen Piper, Felton Timothy, Wang Tao

机构信息

Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK.

Children's Hospital of Chongqing Medical University, Chongqing 400014, China.

出版信息

Biomedicines. 2023 May 18;11(5):1476. doi: 10.3390/biomedicines11051476.

DOI:10.3390/biomedicines11051476
PMID:37239147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10216357/
Abstract

Differentiation of induced pluripotent stem cells to a range of target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs and then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, the organoids expressed ACE2 capable of binding SARS-CoV-2 spike proteins, demonstrating the physiological relevance of the organoids produced. This study presented a rapid production of pulmonary organoids using a multi-germ-layer approach that could be used for studying respiratory-related human conditions.

摘要

在单层培养中，诱导多能干细胞向一系列靶细胞类型的分化是普遍存在的。为了进一步改善所产生细胞的表型，三维类器官培养正变得越来越普遍。成熟的类器官通常需要多个胚层的细胞参与。本研究的目的是从确定的内胚层和中胚层祖细胞产生肺类器官。内胚层和中胚层祖细胞从诱导多能干细胞分化而来，然后在三维基质胶水凝胶中组合，并进一步分化14天以产生肺类器官。这些类器官表达了一系列肺细胞标志物，如表面活性蛋白A、表面活性蛋白B、表面活性蛋白C、水通道蛋白5和T1α。此外，这些类器官表达能够结合SARS-CoV-2刺突蛋白的血管紧张素转换酶2，证明了所产生类器官的生理相关性。本研究提出了一种使用多胚层方法快速产生肺类器官的方法，该方法可用于研究与呼吸相关的人类疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ba/10216357/8845c35f4475/biomedicines-11-01476-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ba/10216357/f7527adfe64c/biomedicines-11-01476-g0A3.jpg
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