Myocardial infarction induces embryonic reprogramming of epicardial c-kit+ cells: Role of the pericardial fluid

Limana, Federica; Bertolami, Chiara; Mangoni, Antonella; Carlo, Anna Di; Avitabile, Daniele; Mocini, David; Iannelli, Giuseppina; Mori, Roberta De; Marchetti, Carlo; Pozzoli, Ombretta; Gentili, Carlo; Zacheo, Antonella; Germani, Antonia; Capogrossi, Maurizio C.

doi:10.1016/j.yjmcc.2009.11.008

Cited by 127 publications

(114 citation statements)

References 39 publications

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“…Early studies showed that the adult epicardium is highly reactive to injury and is involved in immune surveillance (Gittenberger-de Groot et al, 2010;Yung and Chan, 2009). It is now clear that the adult epicardium, as for its developmental counterpart, acts as both a progenitor population and a source of pro-angiogenic and other paracrine signals after injury (Limana et al, 2010(Limana et al, , 2007. In both zebrafish and mouse, the epicaridum of injured adult hearts undergoes global activation of its fetal epicardial program Kikuchi et al, 2011;Lepilina et al, 2006;Zhou et al, 2011), and experimental depletion of epicardium in fish leads to its rapid regeneration guided by signals from the outflow tract including Hedgehog ligand (Wang et al, 2015).…”

Section: The Adult Epicardium As a Progenitor Populationmentioning

confidence: 99%

“…In adult mouse hearts subjected to myocardial infarction, epicardial cells undergo EMT and migrate to the subepicardium, where they differentiate into myofibroblasts and smooth muscle cells (but not cardiomyocytes or endothelial cells), which incorporate into new vessels . The epicardium is highly heterogeneous , and a minority KIT + /CD34 + /CD45 − population has been observed to proliferate after injury and differentiate into smooth muscle cells and endothelial cells organized into vessels, with a potential role for pericardial fluid in maintaining their progenitor status (Limana et al, 2010(Limana et al, , 2007. A population of glycolytic progenitors expressing HIF1α has also been described (Kocabas et al, 2012).…”

Section: The Adult Epicardium As a Progenitor Populationmentioning

confidence: 99%

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Developmental origin and lineage plasticity of endogenous cardiac stem cells

et al. 2016

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Over the past two decades, several populations of cardiac stem cells have been described in the adult mammalian heart. For the most part, however, their lineage origins and in vivo functions remain largely unexplored. This Review summarizes what is known about different populations of embryonic and adult cardiac stem cells, including KIT + , PDGFRα + , ISL1 + and SCA1 + cells, side population cells, cardiospheres and epicardial cells. We discuss their developmental origins and defining characteristics, and consider their possible contribution to heart organogenesis and regeneration. We also summarize the origin and plasticity of cardiac fibroblasts and circulating endothelial progenitor cells, and consider what role these cells have in contributing to cardiac repair.

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Section: The Adult Epicardium As a Progenitor Populationmentioning

confidence: 99%

Section: The Adult Epicardium As a Progenitor Populationmentioning

confidence: 99%

Developmental origin and lineage plasticity of endogenous cardiac stem cells

et al. 2016

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“…Many positive effects of EPDCs either after injection or by stimulation of the dormant native epicardial covering of the heart are due to a paracrine mechanism [22,24,25]. These findings bear important potential for drug and cell-based therapeutic approaches to stimulate the native epicardium in repair of the ischemic cardiac wall.…”

Section: Future Directions and Clinical Applicationsmentioning

confidence: 98%

“…Different approaches have focused on the potential of the adult epicardial cell after myocardial infarction (MI). A c-kit-positive subepicardial population indicates renewed epicardial activity with acquisition of stem cell characteristics [22]. Using a retrovirally induced fluorescent Katushka labeling of dormant epicardium showed EPDCs that migrated into the myocardium and differentiated into a myofibroblast phenotype.…”

Section: Cardiovascular Repairmentioning

confidence: 99%

The Arterial Epicardium: A Developmental Approach to Cardiac Disease and Repair

Groot

Winter

Goumans

et al. 2016

Etiology and Morphogenesis of Congenital Heart Disease

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The significance of the epicardium that covers the heart and the roots of the great arteries should not be underestimated as it is a major component with impact on development, disease, and repair. The epicardium differentiates from the proepicardial organ located at the venous pole (vPEO). The differentiation capacities of the vPEO into epicardium-derived cells (EPDCs) have been extensively described. A hitherto escaped part of the epicardium derives from a second proepicardial organ located at the arterial pole (aPEO) and covers the intrapericardial part of the aorta and pulmonary trunk. In avian and mouse embryos, disturbance of epicardium differentiation causes a spectrum of cardiac anomalies including coronary artery abnormalities, deficient annulus fibrosis with rhythm disturbances, valve malformations, and non-compaction cardiomyopathies. Late in prenatal life the epicardium becomes dormant, losing the activity of many genes.In human cardiac diseases, both arterial and venous epicardium can be activated again into EPDCs. The epicardial reactivation observed after experimental

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“…Several molecules have been identified in the pericardial fluid of normal and diseased heart, and their levels correlate with regenerative [92 98] and inflammatory responses [99 102] (Figure 4). Examples include FGFs [92,93], VEGF [92,94,95], hepatocyte growth factor [96], high-mobility group box 1 protein-96 and insulin-like growth factor-1 [96,98]. Growth factors present in pericardial fluid can affect proliferation and differentiation of cardiac progenitors towards myocardial and vascular lineages [103 105].…”

Section: Epicardium and Cardiac Regenerationmentioning

confidence: 99%

Epicardial Lineages and Cardiac Repair

Singh

Epstein

2013

JDB

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Abstract:The death of cardiac myocytes resulting from myocardial infarction is a major cause of heart failure worldwide. Effective therapies for regenerating lost cardiac myocytes are lacking. Recently, the epicardium has been implicated as a source of inflammatory cytokines, growth factors and progenitor cells that modulate the response to myocardial injury. During embryonic development, epicardially-derived cells have the potential to differentiate into multiple cardiac lineages, including fibroblasts, vascular smooth muscle and potentially other cell types. In the healthy adult heart, epicardial cells are thought to be generally quiescent. However, injury of the adult heart results in reactivation of a developmental gene program in the epicardium, which leads to increased epicardial cell proliferation and differentiation of epicardium-derived cells (EPDCs) into various cardiac lineages. Recent work suggests that epicardial reactivation after injury is accompanied by, and contributes to, a robust inflammatory response. In this review, we describe the current status of research related to epicardial biology in cardiac development and regeneration, highlighting important recent discoveries and ongoing controversies.

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Myocardial infarction induces embryonic reprogramming of epicardial c-kit+ cells: Role of the pericardial fluid

Cited by 127 publications

References 39 publications

Developmental origin and lineage plasticity of endogenous cardiac stem cells

Developmental origin and lineage plasticity of endogenous cardiac stem cells

The Arterial Epicardium: A Developmental Approach to Cardiac Disease and Repair

Epicardial Lineages and Cardiac Repair

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