Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease

Atmanli, Ayhan; Domian, Ibrahim J.

doi:10.1016/j.tcb.2016.11.010

Cited by 16 publications

(19 citation statements)

References 135 publications

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“…These scaffolds are mainly aimed at providing mechanical support to the infarcted area, which minimizes cardiac remodeling and helps preserve the contractile function of the heart [10][11][12]. However, the recapitulation of the morphological and physiological features of the native myocardium remains challenging due to the complexity of structural, biochemical, and biophysical properties of the native cardiac microenvironment [13]. For instance, these https://doi.org/10.1016/j.biomaterials.2019.03.015 Received 18 September 2018; Received in revised form 8 March 2019; Accepted 13 March 2019 scaffolds should exhibit high durability and mechanical resilience to withstand repeated cycles of stretching during cardiac beating [14].…”

Section: Introductionmentioning

confidence: 99%

Engineering a naturally-derived adhesive and conductive cardiopatch

et al. 2019

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Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

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Section: Introductionmentioning

confidence: 99%

Engineering a naturally-derived adhesive and conductive cardiopatch

et al. 2019

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“…Taken together, our data show that YAP masks a previously unknown direct route toward cardiac mesoderm formation in hESCs. These findings may be exploited in the future to facilitate cardiac differentiation procedures for use in regenerative stem cell therapies (Atmanli and Domian 2017;Duelen and Sampaolesi 2017).…”

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confidence: 98%

YAP repression of the WNT3 gene controls hESC differentiation along the cardiac mesoderm lineage

et al. 2017

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Activin/SMAD signaling in human embryonic stem cells (hESCs) ensures expression and stem cell pluripotency. In the presence of Wnt ligand, the Activin/SMAD transcription network switches to cooperate with Wnt/β-catenin and induce mesendodermal (ME) differentiation genes. We show here that the Hippo effector YAP binds to the gene enhancer and prevents the gene from being induced by Activin in proliferating hESCs. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) data show that YAP impairs SMAD recruitment and the accumulation of P-TEFb-associated RNA polymerase II (RNAPII) C-terminal domain (CTD)-Ser7 phosphorylation at the gene. CRISPR/ knockout of YAP in hESCs enables Activin to induce Wnt3 expression and stabilize β-catenin, which then synergizes with Activin-induced SMADs to activate a subset of ME genes that is required to form cardiac mesoderm. Interestingly, exposure of YAP hESCs to Activin induces cardiac mesoderm markers ( and ) without activating Wnt-dependent cardiac inhibitor genes ( and ). Moreover, canonical Wnt target genes are up-regulated only modestly, if at all, under these conditions. Consequently, YAP-null hESCs exposed to Activin differentiate precisely into beating cardiomyocytes without further treatment. We conclude that YAP maintains hESC pluripotency by preventing expression in response to Activin, thereby blocking a direct route to embryonic cardiac mesoderm formation.

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“…The cardiac microenvironment constitutes a cardiogenic niche that controls cardiac development, function and disease (Atmanli et al 2017). As mentioned in 'Glucocorticoids in heart development and function' section, supporting cells such as endothelial cells, immune cells and fibroblasts in the cardiac microenvironment are crucial for cardiac development, autoregulation and adaptation.…”

Section: Regulation Of Glucocorticoids On Cardiac Microenvironmentmentioning

confidence: 99%

Glucocorticoids and programming of the microenvironment in heart

Song

Zhang

2019

Journal of Endocrinology

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Glucocorticoids are primary stress hormones and can improve neonatal survival when given to pregnant women threatened by preterm birth or to preterm infants. It has become increasingly apparent that glucocorticoids, primarily by interacting with glucocorticoid receptors, play a critical role in late gestational cardiac maturation. Altered glucocorticoid actions contribute to the development and progression of heart disease. The knowledge gained from studies in the mature heart or cardiac damage is insufficient but a necessary starting point for understanding cardiac programming including programming of the cardiac microenvironment by glucocorticoids in the fetal heart. This review aims to highlight the potential roles of glucocorticoids in programming of the cardiac microenvironment, especially the supporting cells including endothelial cells, immune cells and fibroblasts. The molecular mechanisms by which glucocorticoids regulate the various cellular and extracellular components and the clinical relevance of glucocorticoid functions in the heart are also discussed.

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Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease

Cited by 16 publications

References 135 publications

Engineering a naturally-derived adhesive and conductive cardiopatch

Engineering a naturally-derived adhesive and conductive cardiopatch

YAP repression of the WNT3 gene controls hESC differentiation along the cardiac mesoderm lineage

Glucocorticoids and programming of the microenvironment in heart

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