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Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis?
Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakth...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678132/ https://www.ncbi.nlm.nih.gov/pubmed/26666881 http://dx.doi.org/10.1186/s40348-015-0023-5 |
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author | Martin, Ulrich |
author_facet | Martin, Ulrich |
author_sort | Martin, Ulrich |
collection | PubMed |
description | Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakthrough is visible for the majority of patients suffering from cystic fibrosis (CF). Novel compounds have to be identified and tailored in combination to specific CFTR mutations, to different tissues, or even to the individual patient. Immortalized cell lines overexpressing mutant CFTR are typically used to screen candidate molecules but have proven to be poor predictors of clinical efficacy. The complexity of CFTR maturation and turnover requires the use of cellular models that closely recapitulate the specific properties of the clinically most affected organs. Importantly, current screening efforts based on primary airway cells or intestinal organoids cannot specifically target single rare CFTR mutations or mimic multiple cell types. In the near future, genetically engineered induced pluripotent stem cells will provide an excellent basis for personalized organotypic models of CF disease and biological screens for identification of CFTR potentiators and correctors. |
format | Online Article Text |
id | pubmed-4678132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-46781322015-12-22 Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? Martin, Ulrich Mol Cell Pediatr Minireview Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakthrough is visible for the majority of patients suffering from cystic fibrosis (CF). Novel compounds have to be identified and tailored in combination to specific CFTR mutations, to different tissues, or even to the individual patient. Immortalized cell lines overexpressing mutant CFTR are typically used to screen candidate molecules but have proven to be poor predictors of clinical efficacy. The complexity of CFTR maturation and turnover requires the use of cellular models that closely recapitulate the specific properties of the clinically most affected organs. Importantly, current screening efforts based on primary airway cells or intestinal organoids cannot specifically target single rare CFTR mutations or mimic multiple cell types. In the near future, genetically engineered induced pluripotent stem cells will provide an excellent basis for personalized organotypic models of CF disease and biological screens for identification of CFTR potentiators and correctors. Springer Berlin Heidelberg 2015-12-14 /pmc/articles/PMC4678132/ /pubmed/26666881 http://dx.doi.org/10.1186/s40348-015-0023-5 Text en © Martin. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Minireview Martin, Ulrich Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
title | Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
title_full | Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
title_fullStr | Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
title_full_unstemmed | Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
title_short | Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
title_sort | pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis? |
topic | Minireview |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678132/ https://www.ncbi.nlm.nih.gov/pubmed/26666881 http://dx.doi.org/10.1186/s40348-015-0023-5 |
work_keys_str_mv | AT martinulrich pluripotentstemcellsfordiseasemodelinganddrugscreeningnewperspectivesfortreatmentofcysticfibrosis |