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Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis

The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over th...

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Autores principales: Silva, Iris A. L., Laselva, Onofrio, Lopes-Pacheco, Miquéias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409685/
https://www.ncbi.nlm.nih.gov/pubmed/36013270
http://dx.doi.org/10.3390/jpm12081321
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author Silva, Iris A. L.
Laselva, Onofrio
Lopes-Pacheco, Miquéias
author_facet Silva, Iris A. L.
Laselva, Onofrio
Lopes-Pacheco, Miquéias
author_sort Silva, Iris A. L.
collection PubMed
description The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over the last 30 years and they have been instrumental not only in enhancing the understanding of CF pathological mechanisms but also in developing therapies targeting the underlying defects in CFTR mutations with further validation in patient-derived samples. Furthermore, recent advances toward precision medicine in CF have been made possible by optimizing protocols and establishing novel assays using human bronchial, nasal and rectal tissues, and by progressing from two-dimensional monocultures to more complex three-dimensional culture platforms. These models also enable to potentially predict clinical efficacy and responsiveness to CFTR modulator therapies at an individual level. In parallel, advanced systems, such as induced pluripotent stem cells and organ-on-a-chip, continue to be developed in order to more closely recapitulate human physiology for disease modeling and drug testing. In this review, we have highlighted novel and optimized cell models that are being used in CF research to develop novel CFTR-directed therapies (or alternative therapeutic interventions) and to expand the usage of existing modulator drugs to common and rare CF-causing mutations.
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spelling pubmed-94096852022-08-26 Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis Silva, Iris A. L. Laselva, Onofrio Lopes-Pacheco, Miquéias J Pers Med Review The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over the last 30 years and they have been instrumental not only in enhancing the understanding of CF pathological mechanisms but also in developing therapies targeting the underlying defects in CFTR mutations with further validation in patient-derived samples. Furthermore, recent advances toward precision medicine in CF have been made possible by optimizing protocols and establishing novel assays using human bronchial, nasal and rectal tissues, and by progressing from two-dimensional monocultures to more complex three-dimensional culture platforms. These models also enable to potentially predict clinical efficacy and responsiveness to CFTR modulator therapies at an individual level. In parallel, advanced systems, such as induced pluripotent stem cells and organ-on-a-chip, continue to be developed in order to more closely recapitulate human physiology for disease modeling and drug testing. In this review, we have highlighted novel and optimized cell models that are being used in CF research to develop novel CFTR-directed therapies (or alternative therapeutic interventions) and to expand the usage of existing modulator drugs to common and rare CF-causing mutations. MDPI 2022-08-16 /pmc/articles/PMC9409685/ /pubmed/36013270 http://dx.doi.org/10.3390/jpm12081321 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Silva, Iris A. L.
Laselva, Onofrio
Lopes-Pacheco, Miquéias
Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
title Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
title_full Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
title_fullStr Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
title_full_unstemmed Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
title_short Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
title_sort advances in preclinical in vitro models for the translation of precision medicine for cystic fibrosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409685/
https://www.ncbi.nlm.nih.gov/pubmed/36013270
http://dx.doi.org/10.3390/jpm12081321
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