Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias
Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic c...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2012-08-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00346/full |
| _version_ | 1818019373441351680 |
|---|---|
| author | Maaike eHoekstra Christine L. Mummery Arthur A.M. Wilde Connie R. Bezzina Arie O. Verkerk |
| author_facet | Maaike eHoekstra Christine L. Mummery Arthur A.M. Wilde Connie R. Bezzina Arie O. Verkerk |
| author_sort | Maaike eHoekstra |
| collection | DOAJ |
| description | Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic) arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC) has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially) characterized.Human iPSC (hiPSC) models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these disorders. |
| first_indexed | 2024-04-14T07:51:25Z |
| format | Article |
| id | doaj.art-0856561a499d4a259d9a8049e3b33e0c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-14T07:51:25Z |
| publishDate | 2012-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-0856561a499d4a259d9a8049e3b33e0c2022-12-22T02:05:10ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-08-01310.3389/fphys.2012.0034627708Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmiasMaaike eHoekstra0Christine L. Mummery1Arthur A.M. Wilde2Connie R. Bezzina3Arie O. Verkerk4Academic Medical CenterLeiden University Medical CenterAcademic Medical CenterAcademic Medical CenterAcademic Medical CenterCardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic) arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC) has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially) characterized.Human iPSC (hiPSC) models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these disorders.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00346/fullElectrophysiologyHeartInduced Pluripotent Stem Cellshumancardiomyocytescardiac arrhythmia syndromes |
| spellingShingle | Maaike eHoekstra Christine L. Mummery Arthur A.M. Wilde Connie R. Bezzina Arie O. Verkerk Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias Frontiers in Physiology Electrophysiology Heart Induced Pluripotent Stem Cells human cardiomyocytes cardiac arrhythmia syndromes |
| title | Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias |
| title_full | Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias |
| title_fullStr | Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias |
| title_full_unstemmed | Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias |
| title_short | Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias |
| title_sort | induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias |
| topic | Electrophysiology Heart Induced Pluripotent Stem Cells human cardiomyocytes cardiac arrhythmia syndromes |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00346/full |
| work_keys_str_mv | AT maaikeehoekstra inducedpluripotentstemcellderivedcardiomyocytesasmodelsforcardiacarrhythmias AT christinelmummery inducedpluripotentstemcellderivedcardiomyocytesasmodelsforcardiacarrhythmias AT arthuramwilde inducedpluripotentstemcellderivedcardiomyocytesasmodelsforcardiacarrhythmias AT connierbezzina inducedpluripotentstemcellderivedcardiomyocytesasmodelsforcardiacarrhythmias AT arieoverkerk inducedpluripotentstemcellderivedcardiomyocytesasmodelsforcardiacarrhythmias |