Soluble ECM promotes organotypic formation in lung alveolar model.

Autor: Valdoz JC; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Franks NA; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Cribbs CG; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Jacobs DJ; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Dodson EL; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Knight CJ; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Poulson PD; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Garfield SR; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Johnson BC; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Hemeyer BM; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Sudo MT; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Saunooke JA; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Kartchner BC; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Saxton A; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Vallecillo-Zuniga ML; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Santos M; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Chamberlain B; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Christensen KA; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA., Nordin GP; Electrical and Computer Engineering Department, Brigham Young University, Provo, UT, 84602, USA., Narayanan AS; University of Washington, Seattle, WA, 98195, USA., Raghu G; Center for Interstitial Lung Disease, University of Washington 1959, NE Pacific Ave, Seattle, WA, 98195, USA. Electronic address: graghu@uw.edu., Van Ry PM; Chemistry and Biochemistry, Brigham Young University, Ezra Taft Benson Building, Campus Drive, Provo, 84601, UT, USA. Electronic address: pvanry@chem.byu.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2022 Apr; Vol. 283, pp. 121464. Date of Electronic Publication: 2022 Mar 16.
DOI: 10.1016/j.biomaterials.2022.121464
Abstrakt: Micropatterned suspension culture creates consistently sized and shaped cell aggregates but has not produced organotypic structures from stable cells, thus restricting its use in accurate disease modeling. Here, we show that organotypic structure is achieved in hybrid suspension culture via supplementation of soluble extracellular matrix (ECM). We created a viable lung organoid from epithelial, endothelial, and fibroblast human stable cell lines in suspension culture. We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of lumen-like structures with airspace showing feasible gas exchange units, formation of branching, perfusable vasculature, and long-term 70-day maintenance of lumen structure. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We also demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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