Human stem cells as a model for cardiac differentiation and disease

Beqqali, Abdelaziz; Eldik, W. van; Mummery, Christine L.; Passier, Robert

doi:10.1007/s00018-009-8476-0

Cited by 30 publications

(21 citation statements)

References 96 publications

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“…Among the regulatory factors identified in several groups of genes showing similar behavior (early downregulation, early upregulation, regulation during differentiation, fibronectin receptor complex), TGF-ß, TNF and BMP6 were identified. Temporal changes in the transcriptional profile of differentiating human ESC-derived CMs were investigated by Beqqali et al They showed that during differentiation of human ESCs, patterns of gene expression with early upregulation of embryonic genes followed by induction of mesoderm-specific and cardiac-specific genes occurred (25).…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Wojakowski

Tendera²,

Kucia³

et al. 2010

Int J Oncol

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Abstract.VSELs are a population of rare Oct-4 + CXCR4 + CD133 + lin -CD45 -cells that are deposited during early embryogenesis in developing organs/tissues as a reserve population of pluripotent stem cells for regeneration. We reported recently that they are mobilized into peripheral blood during acute myocardial infarction (AMI) in mice and humans. However, although freshly isolated VSELs in experimental AMI mouse models improve cardiac function, the number of these cells is limited and an ex vivo expansion strategy is needed to employ these cells more efficiently for cardiac regeneration. The aim of this study was to establish an efficient method to expand ex vivo BM-derived very small embryonic-like stem cells (VSELs) into cardiomyocytes. VSELs, highly purified by FACS from the bone marrow of GFP transgenic mice, were expanded over C2C12 cell line myoblasts and exposed to cardiac differentiating media. The changes in gene expression during cardiac differentiation of VSELs were evaluated by RTQ-PCR, immunostaining and gene array analysis. We developed an efficient, two-step, ex vivo expansion/differentiation model of BM-derived VSELs into cardiomyocytes. First, purified GFP + VSELs are plated over C2C12 murine cell line myoblasts, where they expand and differentiate into characteristic spheres. Subsequently, cells from these spheres are expanded on cardiac differentiating media into cardiomyocytes. This study demonstrates that murine BM-derived VSELs can be efficiently expanded in vitro and differentiated into cardiomyocytes.

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Section: Discussionmentioning

confidence: 99%

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Wojakowski

Tendera²,

Kucia³

et al. 2010

Int J Oncol

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“…In stem cell research, a growing number of studies have been published the last decade focusing on cardiac regeneration [117,165] and on the pacemaker mechanism [166−172] . As hESCCMs usually start to beat spontaneously between the 9th and 12th day after differentiation begins, we focused our work on young cells (d11 to 21), which parallels the early beating cells of the cardiac tube [173] .…”

Section: The Calcium-activated Potassium Channel Familymentioning

confidence: 99%

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

et al. 2016

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The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cellderived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca 2+ -activated K + channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

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“…ECM components considerably influence the growth characteristics of cardiomyocytes, development of physiological activities such as spontaneous contractile activity and phenotype morphological differentiation, suggesting synergestic effect of ECM components (Bick et al, 1998;. Elementary cardiac differentiation mechanisms have been elucidated using animal models along with in vitro models of cardiac development such as mouse embryonal carcinoma cells, mouse embryonic stem cells and recently, human embryonic stem cells (Kraehenbuehl et al, 2008;Beqqali et al, 2009). The growth rate and adhesion of murine mesenchymal stem cells in cardiogel were found to increase when co-cultured together .…”

Section: Cardiogel Supports Adhesion Proliferation and Differentiatimentioning

confidence: 99%

Cardiogel supports adhesion, proliferation and differentiation of stem cells with increased oxidative stress protection

Sreejit

Rs²

2011

eCM

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Cultured murine bone marrow derived mesenchymal stem cells (BMSC) when grown along with cardiogel derived from mouse cardiac fibroblast, exhibited increased cell proliferation and differentiation and enhanced survival under oxidative stress induced by the exposure of H 2 O 2 in vitro (similar to in vivo ischemia like condition). Adhesion of BMSC to the cardiogel occurred at a faster rate when compared to the cells grown on normal surface. BMSC attached to cardiogel showed an increased resistance to proteolytic (enzymatic) disassociation. This is the first report on an attempt to use an in house biomaterial for the growth of BMSC that led to their heightened resistance towards oxidative stress. These studies support that cardiogel is an efficient biodegradable three-dimensional extracellular matrix which supports better growth of BMSC and can be used as a scaffold for stem cell delivery, with potential therapeutic applications in cardiac tissue regeneration.

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Human stem cells as a model for cardiac differentiation and disease

Cited by 30 publications

References 96 publications

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

Cardiogel supports adhesion, proliferation and differentiation of stem cells with increased oxidative stress protection

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