The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

Wessels, Andy; Pérez‐Pomares, José M.

doi:10.1002/ar.a.10129

Cited by 282 publications

(253 citation statements)

References 125 publications

(146 reference statements)

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“…Instead, the PE and the heart are growing toward each other, allowing for contact to occur and the transfer of PE cells from the area of the septum transversum to the heart, where active cellular migration then occurs over the surface of the primitive myocardium to form the intact epicardium. This cellular outgrowth is likely to be in part due to the high rate of proliferation previously described in several reports (Kuhn and Liebherr, 1988;Wessels and Perez-Pomares, 2004;Hirose et al, 2006).…”

Section: Discussionmentioning

confidence: 70%

Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart

Rodgers

Lalani

Runyan

et al. 2007

Developmental Dynamics

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In the mammalian system the proepicardium (PE) arises from mesothelium of the septum transversum before translocation to the heart where it forms the epicardium and progenitor cells of the coronary vessels. Despite its importance, the process in which PE cells translocate to the myocardium in mammals is not well defined. The current paradigm states that cellular cysts of PE float across the pericardial space and contact the outer surface of the myocardium. This mechanism does not provide a satisfactory explanation for the directionality or localization of PE migration. To better define PE migration, we performed a detailed study of mouse PE development. We provide thorough documentation that redefines the size of the PE migratory field and the mechanism of migration. Our new model incorporates differential growth and direct contact between multicellular PE villi and the myocardium as mechanisms in formation of the epicardium. Developmental Dynamics 237:145-152, 2008.

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Section: Discussionmentioning

confidence: 70%

Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart

Rodgers

Lalani

Runyan

et al. 2007

Developmental Dynamics

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“…Although the meaning of this finding is not yet known, it suggests that this proportionality may be important for efficient hemodynamic function. The growth changes make sense however because previous studies demonstrate a significant amount of tissue volume is being added via proepicardial (both ventricles), neural crest (right ventricle, outflow tracts), and the secondary heart field during this time (Mjaatvedt et al, 2001;Yelbuz et al, 2003;Wessels and Perez-Pomares, 2004). Atrial lumen volumes, in contrast, grew much larger than their respective myocardium.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Three‐Dimensional Analysis of Embryonic Chick Morphogenesis Via Microcomputed Tomography

Kim

Min

Recknagel

et al. 2010

The Anatomical Record

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Embryonic development is a remarkably complex and rapidly evolving morphogenetic process. Although many of the early patterning events have been well described, understanding the anatomical changes at later stages where clinically relevant malformations are more likely to be survivable has been limited by the lack of quantitative 3D imaging tools. Microcomputed tomography (Micro-CT) has emerged as a powerful tool for embryonic imaging, but a quantitative analysis of organ and tissue growth has not been conducted. In this study, we present a simple method for acquiring highly detailed, quantitative 3D datasets of embryonic chicks with Micro-CT. Embryos between 4 and 12 days (HH23 and HH40) were labeled with osmium tetroxide (OT), which revealed highly detailed soft tissue anatomy when scanned at 25 lm resolution. We demonstrate tissue boundary and inter-tissue contrast fidelity in virtual 2D sections are quantitatively and qualitatively similar to those of histological sections. We then establish mathematical relationships for the volumetric growth of heart, limb, eye, and brain during this period of development. We show that some organs exhibit constant exponential growth (eye and heart), whereas others contained multiple phases of growth (forebrain and limb). Furthermore, we show that cardiac myocardial volumetric growth differs in a time and chamber specific manner. These results demonstrate Micro-CT is a powerful technique for quantitative imaging of embryonic growth. The data presented here establish baselines from which to compare the effects of genetic or experimental perturbations. Quantifying subtle differences in morphogenesis is increasingly important as research focuses on localized and conditional effects. Anat Rec, 294:1-10, 2011. V V C 2010 Wiley-Liss, Inc.Key words: quantitative imaging; morphology; embryo; chick; histology quantification; microCT-based virtual histologyCongenital malformations remain a significant cause of death and disability. Although many birth defects have an underlying genetic mutation, the majority of clinical cases are not traceable to a genetic cause (McBride et al., 2005;Clark et al., 2006). Molecular biology based research over the last decade has uncovered numerous transcription factors, signaling networks, and matricellular proteins essential in controlling embryonic morphogenesis (Camenisch et al

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“…Adult valve interstitial cells are derived from epicardially derived mesenchymal cells that invade the endocardial cushions 42 and from cells derived from the embryonic epicardium. 43 Recent reports indicate that circulating hematopoietic stem cells also contribute to adult VIC populations. 41 Notably, adult hematopoietic stem cells have multilineage differential potential to nonhematopoietic lineages, including myofibroblastic 44 and osteogenic.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Aortic Valve Mesenchymal Progenitor Cells with Robust Osteogenic Calcification Potential

Chen

Yip

Sone

et al. 2009

The American Journal of Pathology

186

138

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Advanced valvular lesions often contain ectopic mesenchymal tissues, which may be elaborated by an unidentified multipotent progenitor subpopulation within the valve interstitium. The identity, frequency, and differentiation potential of the putative progenitor subpopulation are unknown. The objectives of this study were to determine whether valve interstitial cells (VICs) contain a subpopulation of multipotent mesenchymal progenitor cells, to measure the frequencies of the mesenchymal progenitors and osteoprogenitors, and to characterize the osteoprogenitor subpopulation because of its potential role in calcific aortic valve disease. The multilineage potential of freshly isolated and subcultured porcine aortic VICs was tested in vitro. Progenitor frequencies and selfrenewal capacity were determined by limiting dilution and colony-forming unit assays. VICs were inducible to osteogenic, adipogenic, chondrogenic, and myofibrogenic lineages. Osteogenic differentiation was also observed in situ in sclerotic porcine leaflets. Primary VICs had strikingly high frequencies of mesenchymal progenitors (48.0 ؎ 5.7%) and osteoprogenitors (44.1 ؎ 12.0%). High frequencies were maintained for up to six population doublings , but decreased after nine population doublings to 28.2 ؎ 9.9% and 5.8 ؎ 1.3% , for mesenchymal progenitors and osteoprogenitors , respectively. We further identified the putative osteoprogenitor subpopulation as morphologically distinct cells that occur at high frequency , self-renew , and elaborate bone matrix from single cells. These findings demonstrate that the aortic valve is rich in a mesenchyma l progenitor cell population that has strong potential to contribute to valve calcification. (Am J Pathol

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The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

Cited by 282 publications

References 125 publications

Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart

Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart

Quantitative Three‐Dimensional Analysis of Embryonic Chick Morphogenesis Via Microcomputed Tomography

Identification and Characterization of Aortic Valve Mesenchymal Progenitor Cells with Robust Osteogenic Calcification Potential

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