Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart
Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular developme...
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doaj-bcb2ad668e2a427d9da3387ca7aacefc2021-07-23T13:47:40ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252021-06-018727210.3390/jcdd8070072Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured HeartEmma Adams0Rachel McCloy1Ashley Jordan2Kaitlin Falconer3Iain M. Dykes4Pharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool L3 3AF, UKPharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool L3 3AF, UKPharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool L3 3AF, UKPharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool L3 3AF, UKPharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool L3 3AF, UKCoronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue.https://www.mdpi.com/2308-3425/8/7/72reprogrammingstem cellregenerative medicineinduced pluripotent stem cellmyocardial infarctionheart failure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emma Adams Rachel McCloy Ashley Jordan Kaitlin Falconer Iain M. Dykes |
spellingShingle |
Emma Adams Rachel McCloy Ashley Jordan Kaitlin Falconer Iain M. Dykes Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart Journal of Cardiovascular Development and Disease reprogramming stem cell regenerative medicine induced pluripotent stem cell myocardial infarction heart failure |
author_facet |
Emma Adams Rachel McCloy Ashley Jordan Kaitlin Falconer Iain M. Dykes |
author_sort |
Emma Adams |
title |
Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart |
title_short |
Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart |
title_full |
Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart |
title_fullStr |
Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart |
title_full_unstemmed |
Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart |
title_sort |
direct reprogramming of cardiac fibroblasts to repair the injured heart |
publisher |
MDPI AG |
series |
Journal of Cardiovascular Development and Disease |
issn |
2308-3425 |
publishDate |
2021-06-01 |
description |
Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue. |
topic |
reprogramming stem cell regenerative medicine induced pluripotent stem cell myocardial infarction heart failure |
url |
https://www.mdpi.com/2308-3425/8/7/72 |
work_keys_str_mv |
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