Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing.

Autor:	Greaney AM; Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Vascular Biology and Therapeutics, Yale University, New Haven, CT 06511, USA. Electronic address: allison.greaney@yale.edu., Adams TS; Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT 06519, USA., Brickman Raredon MS; Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Vascular Biology and Therapeutics, Yale University, New Haven, CT 06511, USA; Medical Scientist Training Program, Yale University, New Haven, CT 06511, USA., Gubbins E; Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA., Schupp JC; Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT 06519, USA., Engler AJ; Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Vascular Biology and Therapeutics, Yale University, New Haven, CT 06511, USA., Ghaedi M; Vascular Biology and Therapeutics, Yale University, New Haven, CT 06511, USA; Department of Anesthesiology, Yale University, New Haven, CT 06510, USA., Yuan Y; Vascular Biology and Therapeutics, Yale University, New Haven, CT 06511, USA; Department of Anesthesiology, Yale University, New Haven, CT 06510, USA., Kaminski N; Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT 06519, USA., Niklason LE; Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA; Vascular Biology and Therapeutics, Yale University, New Haven, CT 06511, USA; Department of Anesthesiology, Yale University, New Haven, CT 06510, USA.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Mar 24; Vol. 30 (12), pp. 4250-4265.e6.
DOI:	10.1016/j.celrep.2020.03.004
Abstrakt:	Cell-based therapies have shown promise for treating myriad chronic pulmonary diseases through direct application of epithelial progenitors or by way of engineered tissue grafts or whole organs. To elucidate environmental effects on epithelial regenerative outcomes in vitro, here, we isolate and culture a population of pharmacologically expanded basal cells (peBCs) from rat tracheas. At peak basal marker expression, we simultaneously split peBCs into four in vitro platforms: organoid, air-liquid interface (ALI), engineered trachea, and engineered lung. Following differentiation, these samples are evaluated using single-cell RNA sequencing (scRNA-seq) and computational pipelines are developed to compare samples both globally and at the population level. A sample of native rat tracheal epithelium is also evaluated by scRNA-seq as a control for engineered epithelium. Overall, this work identifies platform-specific effects that support the use of engineered models to achieve the most physiologic differential outcomes in pulmonary epithelial regenerative applications. Competing Interests: Declaration of Interests L.E.N. is a founder of and shareholder in Humacyte, which is a regenerative medicine company. Humacyte produces engineered blood vessels from allogeneic smooth muscle cells for vascular surgery. L.E.N.’s spouse has equity in Humacyte, and L.E.N. serves on Humacyte’s board of directors. L.E.N. is listed as an inventor on patents that are licensed to Humacyte and that produce royalties for L.E.N. L.E.N. has received an unrestricted research gift to support research in her laboratory at Yale University. Humacyte did not fund these studies and Humacyte did not influence the conduct, description, or interpretation of the findings in this article. N.K. served as a consultant to Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, Optikira, and CohBar over the last 3 years and received non-financial support from MiRagen. N.K. is listed as an inventor on several patents and patent applications, none of which are relevant to this manuscript. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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