More than a Cover: Epicardium as a Novel Source of Cardiac Progenitor Cells

Zhou, Bin; Pu, William T.

doi:10.2217/17460751.3.5.633

Cited by 29 publications

(24 citation statements)

References 20 publications

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“…But recent research has demonstrated that these fields are probably no more than regions of a wider “primary” cardiogenic field (see Abu-Issa and Kirby 2007; Moorman et al 2007; Ma et al 2008; Zhou and Pu 2008; Zhou et al 2008), that are added relatively late in development after the dorsal mesocardium has detached from the body of the embryo and there are no alternative direct routes by which cells can add to the growing heart. The different fields were identified primarily by their embryonic position at various stages of development and by their transient expression of genes such as Islet1 and Fgf10 , but their description as “distinct” heart fields is probably somewhat misleading.…”

Section: Discussionmentioning

confidence: 99%

Phylogeny informs ontogeny: a proposed common theme in the arterial pole of the vertebrate heart

Grimes

Durán

Sans‐Coma

et al. 2010

Evolution and Development

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SUMMARY In chick and mouse embryogenesis, a population of cells described as the secondary heart field (SHF) adds both myocardium and smooth muscle to the developing cardiac outflow tract (OFT). Following this addition, at approximately HH stage 22 in chick embryos, for example, the SHF can be identified architecturally by an overlapping seam at the arterial pole, where beating myocardium forms a junction with the smooth muscle of the arterial system. Previously, using either immunohistochemistry or nitric oxide indicators such as diaminofluorescein 2-diacetate, we have shown that a similar overlapping architecture also exists in the arterial pole of zebrafish and some shark species. However, although recent work suggests that development of the zebrafish OFT may also proceed by addition of a SHF-like population of cells, the presence of a true SHF in zebrafish and in many other developmental biological models remains an open question. We performed a comprehensive morphological study of the OFT of a wide range of vertebrates. Our data suggest that all vertebrates possess three fundamental OFT components: a proximal myocardial component, a distal smooth muscle component, and a middle component that contains overlapping myocardium and smooth muscle surrounding and supporting the outflow valves. Because the middle OFT component of avians and mammals is derived from the SHF, our observations suggest that a SHF may be an evolutionarily conserved theme in vertebrate embryogenesis.

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Section: Discussionmentioning

confidence: 99%

Phylogeny informs ontogeny: a proposed common theme in the arterial pole of the vertebrate heart

Grimes

Durán

Sans‐Coma

et al. 2010

Evolution and Development

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“…Although it has been suggested that adult epicardial cells lose their ability to undergo EMT during later stages of embryogenesis (20), considerable evidence supports the possibility that the epicardium can serve as a source of vascular progenitors for cell based therapies (1,6). Altogether, if these pathways also regulate progenitor cells in the adult epicardium, understanding the signaling molecules regulating RhoA activity that function to maintain the progenitor phenotype of the embryonic epicardium might eventually lead to their manipulation in order to facilitate a robust and stable neovascularization or myocardial regeneration of the injured adult heart (7).…”

Section: Epac Activation Suppresses and Partial Silencing Of Epac Enhmentioning

confidence: 99%

“…The adult epicardium is a potential source of smooth muscle cells (SMCs) 3 and pericytes for revascularization after infarction (5). Exciting developments support the possibility that the epicardium can serve as a source of vascular progenitors for cell based therapies (1,6). This is well illustrated in a study showing that thymosin ␤4 activates adult epicardial derived cells and facilitates a robust and stable neovascularization of the injured adult heart (7).…”

mentioning

confidence: 99%

Signaling Pathways That Control Rho Kinase Activity Maintain the Embryonic Epicardial Progenitor State

Artamonov

Jin

Franke

et al. 2015

Journal of Biological Chemistry

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Background: Epicardial cells are a potential source of progenitor cells for revascularization of the injured heart. Results: Decreased p63RhoGEF and GEF-H1 and increased Epac, p190RhoGAP, and Rnds activities suppress RhoA signaling in epicardial progenitors. Conclusion:The embryonic epicardial progenitor state is maintained by signaling pathways that control RhoA activity. Significance: Manipulation of these signaling molecules might promote cardiac revascularization.

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“…To test the hypothesis, we initially examined CBP/p300 differential coactivator usage by β-catenin in vitro, particularly in regards to effects on the epicardium, which has been demonstrated to play an important role in contributing to both cardiac development and regeneration [16], [17]. Finally, we examined if specific β-catenin/CBP inhibition using ICG-001 has a beneficial effect in a rat model of myocardial infarction.…”

Section: Introductionmentioning

confidence: 99%

The Small Molecule Wnt Signaling Modulator ICG-001 Improves Contractile Function in Chronically Infarcted Rat Myocardium

et al. 2013

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The adult mammalian heart has limited capability for self-repair after myocardial infarction. Therefore, therapeutic strategies that improve post-infarct cardiac function are critically needed. The small molecule ICG-001 modulates Wnt signaling and increased the expression of genes beneficial for cardiac regeneration in epicardial cells. Lineage tracing experiments, demonstrated the importance of β-catenin/p300 mediated transcription for epicardial progenitor contribution to the myocardium. Female rats given ICG-001 for 10 days post-occlusion significantly improved ejection fraction by 8.4%, compared to controls (P<0.05). Taken together, Wnt modulation via β-catenin/CBP inhibition offers a promising therapeutic strategy towards restoration of myocardial tissues and an enhancement of cardiac functions following infarction.

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More than a Cover: Epicardium as a Novel Source of Cardiac Progenitor Cells

Cited by 29 publications

References 20 publications

Phylogeny informs ontogeny: a proposed common theme in the arterial pole of the vertebrate heart

Phylogeny informs ontogeny: a proposed common theme in the arterial pole of the vertebrate heart

Signaling Pathways That Control Rho Kinase Activity Maintain the Embryonic Epicardial Progenitor State

The Small Molecule Wnt Signaling Modulator ICG-001 Improves Contractile Function in Chronically Infarcted Rat Myocardium

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