Mechanical control of cell biology. Effects of cyclic mechanical stretch on cardiomyocyte cellular organization

Dhein, Stefan; Schreiber, Anna; Steinbach, Sabine; Apel, Daniel; Salameh, Aida; Schlegel, Franziska; Kostelka, Martin; Dohmen, Pascal M.; Mohr, Friedrich W.

doi:10.1016/j.pbiomolbio.2014.06.006

Cited by 55 publications

(32 citation statements)

References 32 publications

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“…Similar to our results, Cx30 expression in astrocytes led to abnormalities in cellular polarization, β1 integrin redistribution and astrocyte migration, in a process independent of gap junctions [23]. In cardiomyocytes subjected to stretch, Cx43 is overexpressed and the cells spread and polarize their Golgi apparatus to one of the newly formed poles, which contains patches of Cx43 [24]. Taken together, these observations suggest that Cx43 and other Cxs participate in cellular polarization in different types of cells, and not only in astrocytes.…”

Section: Discussionsupporting

confidence: 79%

Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

Lagos-Cabré

Brenet

Díaz

et al. 2018

IJMS

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Under pro-inflammatory conditions, astrocytes become reactive and acquire a migratory phenotype. Our results show that hemichannels formed by connexin 43 (Cx43) play an important role in Thy-1-induced astrocyte migration. The neuronal protein Thy-1 binds to αvβ3 integrin in astrocytes, thereby leading to intricate signaling pathways that include calcium (Ca2+) release from intracellular stores, opening of Cx43 hemichannels, release of ATP, activation of P2X7 receptor, and Ca2+ influx. However, because these Thy-1 effects occur exclusively in reactive astrocytes, we wondered whether by elevating calcium levels and promoting hemichannel opening we could prompt non-reactive astrocytes to respond to Thy-1. Cx43 immunoreactivity increased at juxta-membrane sites, where hemichannels (not gap junctions) participate in astrocyte polarization and migration stimulated by Thy-1. Also, intracellular Ca2+ increase, due to ionomycin treatment, induced hemichannel opening, but activated astrocyte migration only partially, and this limitation was overcome by pre-treatment with tumor necrosis factor (TNF) and Thy-1. Finally, αvβ3 integrin formed membrane clusters after TNF stimulation or overexpression of β3 integrin. We suggest that these microclusters are required for cells to respond to Thy-1 stimulation. Therefore, the large increase in intracellular Ca2+ and hemichannel opening induced by ionomycin are required, but not sufficient, to permit Thy-1-induced astrocyte migration. Thus, we suggest that proinflammatory stimuli prompt astrocytes to respond to migratory signals of neuronal cells.

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Section: Discussionsupporting

confidence: 79%

Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

Lagos-Cabré

Brenet

Díaz

et al. 2018

IJMS

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“…2C) mimics the cyclic filling of the ventricles with blood during diastole making this type of mechanical stimulation more relevant to cardiac muscle as compared to step-wise stretch. Many investigations have shown that dynamic stretch affects intracellular organization, intra- and extracellular tension, FA formation, gene expression, and protein expression [63,139,140,146,150,201,208,209, 250–253]. Commercially available systems have been designed to allow for mechanical stimulation of cells plated on top of elastic substrates (Flexcell International, Inc. [254,255]).…”

Section: Mechanical Stimulation Of Cardiac Cells and Tissuesmentioning

confidence: 99%

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Stoppel

Kaplan

Black

2016

Advanced Drug Delivery Reviews

225

190

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The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro.

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“…Moreover, upscaling for mass stimulation is either difficult or requires high level of power consumption 18 . As an important complement, mechanical stimulation can promote CM maturation, with cyclic mechanical stress applied by external stretching devices capable of forcing muscle-cell assembly into structurally and functionally aligned 3D syncytium 21 , thereby affecting their gene expression 22–24 and Ca 2+ cycling 25 .…”

Section: Introductionmentioning

confidence: 99%

Rapid pacing by circulating traveling waves improves maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

Zhang

et al. 2019

Preprint

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30Directed differentiation methods allow acquisition of high-purity cardiomyocytes (CMs) 31 differentiated from human induced pluripotent stem cells (hiPSCs); however, their 32 immaturity characteristic limits their application for drug screening and regenerative therapy. 33 The rapid electrical pacing of cardiomyocytes have been used for efficiently promoting the 34 maturation of cardiomyocytes, here we describe a simple device in modified culture plate on 35 which hiPSC-derived CMs (hiPSC-CMs) can form three-dimensional self-organized tissue 36 rings (SOTRs). Using calcium imaging, we show that within the ring, traveling waves (TWs) 37 of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 38 2 weeks, SOTRs with TW training showed matured features including structural organization, 39 increased cardiac-specific gene expression, enhanced Ca 2+ -handling properties, an increased 40 oxygen-consumption rate, and enhanced contractile force. We subsequently used a 41 mathematical model to interpret the origination, propagation, and long-term behavior of the 42 TWs within the SOTRs. This new idea for spontaneous hiPSC-CM maturation also has 43 potential for pacing the electrical excitable cells such as neuron and retina cells for various 44 applications. 45 46 47 48

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Mechanical control of cell biology. Effects of cyclic mechanical stretch on cardiomyocyte cellular organization

Cited by 55 publications

References 32 publications

Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Rapid pacing by circulating traveling waves improves maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

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