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Alsafadi, H.N. ; Uhl, F.E.* ; Pineda, R.H.* ; Bailey, K.E.* ; Rojas, M.* ; Wagner, D.E. ; Königshoff, M.

Applications and approaches for three-dimensional precision-cut lung slices disease modeling and drug discovery.

Am. J. Respir. Cell Mol. Biol. 62, 681-691 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targets and therapies are needed. Precision-cut lung slices (PCLS) from healthy and diseased human tissue represent one promising tool that can closely recapitulate the complexity of the lung's native environment, and recently, improved methodologies and accessibility to human tissue have led to an increased use of PCLS in CLD research. Here, we discuss approaches that use human PCLS to advance our understanding of CLD development, as well as drug discovery and validation for CLDs. PCLS enable investigators to study complex interactions among different cell types and the extracellular matrix in the native three-dimensional architecture of the lung. PCLS further allow for high-resolution (live) imaging of cellular functions in several dimensions. Importantly, PCLS can be derived from diseased lung tissue upon lung surgery or transplantation, thus allowing the study of CLDs in living human tissue. Moreover, CLDs can be modeled in PCLS derived from normal lung tissue to mimic the onset and progression of CLDs, complementing studies in end-stage diseased tissue. Altogether, PCLS are emerging as a remarkable tool to further bridge the gap between target identification and translation into clinical studies, and thus open novel avenues for future precision medicine approaches.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Pcls ; Ex Vivo Lung Disease ; Drug Discovery ; Translation; Cigarette-smoke; Animal-models; Tissue; Fibrosis; Airway; Activation; Cell; Bronchoconstriction; Nanoparticles; Pirfenidone
ISSN (print) / ISBN 1044-1549
e-ISSN 1535-4989
Journal American Journal of Respiratory Cell and Molecular Biology
Quellenangaben Volume: 62, Issue: 6, Pages: 681-691 Article Number: , Supplement: ,
Publisher American Thoracic Society
Publishing Place 25 Broadway, 18 Fl, New York, Ny 10004 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Lung Repair and Regeneration (LRR)