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Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for in vitro modelling of diseases with broad application in drug development or toxicology testing. These assays usually require large quantities of hiPSC, which can entail long-term storage via cryopreservation of the sa...

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Autores principales: Khan, Dilaware, Nickel, Ann-Christin, Jeising, Sebastian, Uhlmann, Constanze, Muhammad, Sajjad, Hänggi, Daniel, Fischer, Igor, Kahlert, Ulf Dietrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466661/
https://www.ncbi.nlm.nih.gov/pubmed/34577619
http://dx.doi.org/10.3390/ph14090919
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author Khan, Dilaware
Nickel, Ann-Christin
Jeising, Sebastian
Uhlmann, Constanze
Muhammad, Sajjad
Hänggi, Daniel
Fischer, Igor
Kahlert, Ulf Dietrich
author_facet Khan, Dilaware
Nickel, Ann-Christin
Jeising, Sebastian
Uhlmann, Constanze
Muhammad, Sajjad
Hänggi, Daniel
Fischer, Igor
Kahlert, Ulf Dietrich
author_sort Khan, Dilaware
collection PubMed
description Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for in vitro modelling of diseases with broad application in drug development or toxicology testing. These assays usually require large quantities of hiPSC, which can entail long-term storage via cryopreservation of the same cell charges. However, it is essential that cryopreservation does not oppose durable changes on the cells. In this project, we characterize one parameter of functionality of one that is well established in the field, in a different research context, an applied hiPSC line (iPS11), namely their resistance to a medium size library of chemo interventions (>160 drugs). We demonstrate that cells, before and after cryopreservation, do not change their relative overall drug response phenotypes, as defined by identification of the top 20 interventions causing dose-dependent reduction of cell growth. Importantly, also frozen cells that are exogenously enforced for stable overexpression of oncogenes myelocytomatosis (cMYC) or tumor protein 53 mutation (TP53R175H), respectively, are not changed in their relative top 20 drugs response compared to their non-frozen counterparts. Taken together, our results support iPSCs as a reliable in vitro platform for in vitro pharmacology, further raising hopes that this technology supports biomarker-associated drug development. Given the general debate on ethical and economic problems associated with the reproducibly crisis in biomedicine, our results may be of interest to a wider audience beyond stem cell research.
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spelling pubmed-84666612021-09-27 Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells Khan, Dilaware Nickel, Ann-Christin Jeising, Sebastian Uhlmann, Constanze Muhammad, Sajjad Hänggi, Daniel Fischer, Igor Kahlert, Ulf Dietrich Pharmaceuticals (Basel) Communication Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for in vitro modelling of diseases with broad application in drug development or toxicology testing. These assays usually require large quantities of hiPSC, which can entail long-term storage via cryopreservation of the same cell charges. However, it is essential that cryopreservation does not oppose durable changes on the cells. In this project, we characterize one parameter of functionality of one that is well established in the field, in a different research context, an applied hiPSC line (iPS11), namely their resistance to a medium size library of chemo interventions (>160 drugs). We demonstrate that cells, before and after cryopreservation, do not change their relative overall drug response phenotypes, as defined by identification of the top 20 interventions causing dose-dependent reduction of cell growth. Importantly, also frozen cells that are exogenously enforced for stable overexpression of oncogenes myelocytomatosis (cMYC) or tumor protein 53 mutation (TP53R175H), respectively, are not changed in their relative top 20 drugs response compared to their non-frozen counterparts. Taken together, our results support iPSCs as a reliable in vitro platform for in vitro pharmacology, further raising hopes that this technology supports biomarker-associated drug development. Given the general debate on ethical and economic problems associated with the reproducibly crisis in biomedicine, our results may be of interest to a wider audience beyond stem cell research. MDPI 2021-09-11 /pmc/articles/PMC8466661/ /pubmed/34577619 http://dx.doi.org/10.3390/ph14090919 Text en © 2021 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 Communication
Khan, Dilaware
Nickel, Ann-Christin
Jeising, Sebastian
Uhlmann, Constanze
Muhammad, Sajjad
Hänggi, Daniel
Fischer, Igor
Kahlert, Ulf Dietrich
Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells
title Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells
title_full Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells
title_fullStr Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells
title_full_unstemmed Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells
title_short Testing the Stability of Drug Resistance on Cryopreserved, Gene-Engineered Human Induced Pluripotent Stem Cells
title_sort testing the stability of drug resistance on cryopreserved, gene-engineered human induced pluripotent stem cells
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466661/
https://www.ncbi.nlm.nih.gov/pubmed/34577619
http://dx.doi.org/10.3390/ph14090919
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