Effectiveness of gene delivery systems for pluripotent and differentiated cells
Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) assert a great future for the cardiovascular diseases, both to study them and to explore therapies. However, a comprehensive assessment of the viral vectors used to modify these cells is lacking. In this study, we aimed to...
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Nature Publishing Group
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449028/ |
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pubmed-44490282015-06-05 Effectiveness of gene delivery systems for pluripotent and differentiated cells Rapti, Kleopatra Stillitano, Francesca Karakikes, Ioannis Nonnenmacher, Mathieu Weber, Thomas Hulot, Jean-Sebastian Hajjar, Roger J Article Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) assert a great future for the cardiovascular diseases, both to study them and to explore therapies. However, a comprehensive assessment of the viral vectors used to modify these cells is lacking. In this study, we aimed to compare the transduction efficiency of recombinant adeno-associated vectors (AAV), adenoviruses and lentiviral vectors in hESC, hiPSC, and the derived cardiomyocytes. In undifferentiated cells, adenoviral and lentiviral vectors were superior, whereas in differentiated cells AAV surpassed at least lentiviral vectors. We also tested four AAV serotypes, 1, 2, 6, and 9, of which 2 and 6 were superior in their transduction efficiency. Interestingly, we observed that AAVs severely diminished the viability of undifferentiated cells, an effect mediated by induction of cell cycle arrest genes and apoptosis. Furthermore, we show that the transduction efficiency of the different viral vectors correlates with the abundance of their respective receptors. Finally, adenoviral delivery of the calcium-transporting ATPase SERCA2a to hESC and hiPSC-derived cardiomyocytes successfully resulted in faster calcium reuptake. In conclusion, adenoviral vectors prove to be efficient for both differentiated and undifferentiated lines, whereas lentiviral vectors are more applicable to undifferentiated cells and AAVs to differentiated cells. Nature Publishing Group 2015-02-18 /pmc/articles/PMC4449028/ /pubmed/26052535 http://dx.doi.org/10.1038/mtm.2014.67 Text en Copyright © 2015 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Rapti, Kleopatra Stillitano, Francesca Karakikes, Ioannis Nonnenmacher, Mathieu Weber, Thomas Hulot, Jean-Sebastian Hajjar, Roger J |
| spellingShingle |
Rapti, Kleopatra Stillitano, Francesca Karakikes, Ioannis Nonnenmacher, Mathieu Weber, Thomas Hulot, Jean-Sebastian Hajjar, Roger J Effectiveness of gene delivery systems for pluripotent and differentiated cells |
| author_facet |
Rapti, Kleopatra Stillitano, Francesca Karakikes, Ioannis Nonnenmacher, Mathieu Weber, Thomas Hulot, Jean-Sebastian Hajjar, Roger J |
| author_sort |
Rapti, Kleopatra |
| title |
Effectiveness of gene delivery systems for pluripotent and differentiated cells |
| title_short |
Effectiveness of gene delivery systems for pluripotent and differentiated cells |
| title_full |
Effectiveness of gene delivery systems for pluripotent and differentiated cells |
| title_fullStr |
Effectiveness of gene delivery systems for pluripotent and differentiated cells |
| title_full_unstemmed |
Effectiveness of gene delivery systems for pluripotent and differentiated cells |
| title_sort |
effectiveness of gene delivery systems for pluripotent and differentiated cells |
| description |
Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) assert a great future for the cardiovascular diseases, both to study them and to explore therapies. However, a comprehensive assessment of the viral vectors used to modify these cells is lacking. In this study, we aimed to compare the transduction efficiency of recombinant adeno-associated vectors (AAV), adenoviruses and lentiviral vectors in hESC, hiPSC, and the derived cardiomyocytes. In undifferentiated cells, adenoviral and lentiviral vectors were superior, whereas in differentiated cells AAV surpassed at least lentiviral vectors. We also tested four AAV serotypes, 1, 2, 6, and 9, of which 2 and 6 were superior in their transduction efficiency. Interestingly, we observed that AAVs severely diminished the viability of undifferentiated cells, an effect mediated by induction of cell cycle arrest genes and apoptosis. Furthermore, we show that the transduction efficiency of the different viral vectors correlates with the abundance of their respective receptors. Finally, adenoviral delivery of the calcium-transporting ATPase SERCA2a to hESC and hiPSC-derived cardiomyocytes successfully resulted in faster calcium reuptake. In conclusion, adenoviral vectors prove to be efficient for both differentiated and undifferentiated lines, whereas lentiviral vectors are more applicable to undifferentiated cells and AAVs to differentiated cells. |
| publisher |
Nature Publishing Group |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449028/ |
| _version_ |
1613229473758445568 |