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

作者全名："Mitchell, Adam; Yu, Chaowen; Zhao, Xiangjun; Pearmain, Laurence; Shah, Rajesh; Hanley, Karen Piper; Felton, Timothy; Wang, Tao"

作者地址："[Mitchell, Adam; Yu, Chaowen; Zhao, Xiangjun; Wang, Tao] Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Evolut Infect & Genom, Manchester M13 9PL, England; [Yu, Chaowen] Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China; [Pearmain, Laurence; Hanley, Karen Piper] Univ Manchester, Fac Biol Med & Hlth, Wellcome Trust Ctr Cell Matrix Res, Sch Med Sci,Div Diabet Endocrinol & Gastroenterol, Manchester M13 9PL, England; [Shah, Rajesh] Manchester Univ Hosp NHS Fdn Trust, Wythenshawe Hosp, Southmoor Rd, Manchester M23 9LT, England; [Felton, Timothy] Univ Manchester, Lydia Becker Inst Immunol & Inflammat, Fac Biol Med & Hlth, Div Infect Immun & Resp Med, Manchester M13 9PL, England"

通信作者："Wang, T (通讯作者)，Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Evolut Infect & Genom, Manchester M13 9PL, England.; Felton, T (通讯作者)，Univ Manchester, Lydia Becker Inst Immunol & Inflammat, Fac Biol Med & Hlth, Div Infect Immun & Resp Med, Manchester M13 9PL, England."

来源：BIOMEDICINES

ESI学科分类：　

WOS号：WOS:001011374600001

JCR分区：Q1

影响因子：3.9

年份：2023

卷号：11

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：pulmonary organoids; induced pluripotent stem cells (iPSCs); anterior foregut endoderm; mesoderm; alveoli epithelial cells; SARS-CoV-2; iPSC disease modelling

摘要："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 T1a. 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."

基金机构："North West Lung Centre Charity at Manchester University NHS Foundation Trust [LT038]; China Scholarship Council [201908500055]; Medical Research Council [MR/P023541/1, MR/R00191X/1]"

基金资助正文："This report is independent research supported by the North West Lung Centre Charity at Manchester University NHS Foundation Trust (Ref: LT038). C.Y. is supported by a Post-Doctoral Fellowship from the China Scholarship Council (ref No. 201908500055). K.P.H. and L.P. are supported by The Medical Research Council (K.P.H., MR/P023541/1 and L.P., MR/R00191X/1). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the North West Lung Centre Charity or the Department of Health."