Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering
Colin R. Butler,Robert E. Hynds,Kate H.C. Gowers,Dani Do Hyang Lee,James Brown,Claire Crowley,Vitor H. Teixeira,Claire Smith,Luca Urbani,Nicholas Hamilton,Ricky Thakrar,Helen Booth,Martin A. Birchall,Paolo De Coppi,Adam Giangreco,Christopher O'Callaghan,Sam M. Janes +16 more
TLDR
The authors' method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction.Abstract:
Rationale: Stem cell–based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell–seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts.Objectives: To define a scalable cell culture system to deliver airway epithelium to clinical grafts.Methods: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quant...read more
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Lung organoids: current uses and future promise.
Christina E. Barkauskas,Mei-I Chung,Bryan A. Fioret,Xia Gao,Hiroaki Katsura,Brigid L.M. Hogan +5 more
TL;DR: This Review summarizes the different methods for generating organoids from cells isolated from human and mouse lungs, and compares their final structure and cellular composition with that of the airways or alveoli of the adult lung.
Journal ArticleDOI
Tobacco smoking and somatic mutations in human bronchial epithelium
Kenichi Yoshida,Kate H.C. Gowers,Henry Lee-Six,Deepak P. Chandrasekharan,Tim H. H. Coorens,Elizabeth F. Maughan,Kathryn Beal,Andrew Menzies,Fraser R. Millar,Elizabeth Anderson,Sarah E. Clarke,Adam Pennycuick,Ricky Thakrar,Ricky Thakrar,Colin R. Butler,Colin R. Butler,Nobuyuki Kakiuchi,Tomonori Hirano,Robert E. Hynds,Michael R. Stratton,Inigo Martincorena,Sam M. Janes,Sam M. Janes,Peter J. Campbell,Peter J. Campbell +24 more
TL;DR: W Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelia with near-normal cells.
Journal ArticleDOI
Conditional reprogramming and long-term expansion of normal and tumor cells from human biospecimens
Xuefeng Liu,Ewa Krawczyk,Frank A. Suprynowicz,Nancy Palechor-Ceron,Hang Yuan,Aleksandra Dakic,Vera Simic,Yun-Ling Zheng,Praathibha Sripadhan,Chen Chen,Jie Lu,Tung-Wei Hou,Sujata Choudhury,Bhaskar Kallakury,Dean G. Tang,Thomas N. Darling,Rajesh L. Thangapazham,Olga A. Timofeeva,Anatoly Dritschilo,Scott H. Randell,Christopher Albanese,Seema Agarwal,Richard Schlegel +22 more
TL;DR: Conditional reprogramming (CR) is described, which involves coculture of irradiated mouse fibroblast feeder cells with normal and tumor human epithelial cells in the presence of a Rho kinase inhibitor (Y-27632).
Journal ArticleDOI
Organoid technology and applications in cancer research
TL;DR: In conclusion, organoids represent an excellent preclinical model for human tumors, promoting the translation from basic cancer research to clinical practice and its applications in cancer research are summarized.
Journal ArticleDOI
Differentiated human airway organoids to assess infectivity of emerging influenza virus
Jie Zhou,Cun Li,Norman Sachs,Man Chun Chiu,Bosco Ho-Yin Wong,Hin Chu,Vincent Kwok-Man Poon,Dong Wang,Xiaoyu Zhao,Lei Wen,Wenjun Song,Wenjun Song,Shuofeng Yuan,Kenneth K. Y. Wong,Jasper Fuk-Woo Chan,Kelvin K. W. To,Honglin Chen,Hans Clevers,Kwok-Yung Yuen +18 more
TL;DR: The proximal differentiated airway organoids can be utilized to predict the infectivity of influenza viruses and, more broadly, provide a universal platform for studying the biology and pathology of the human airway.
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