Investigation of cardiac fibroblasts using myocardial slices

Perbellini, Filippo; Watson, Samuel A.; Scigliano, Martina; Alayoubi, Samha; Tkach, S.I.; Bardi, Ifigeneia; Quaife, Nicholas M; Kane, Christopher; Dufton, Neil; Simón, A.; Sikkel, Markus B.; Faggian, Giuseppe; Randi, Anna M.; Gorelik, Julia; Harding, Siân E.; Terracciano, Cesare M.

doi:10.1093/cvr/cvx152

Cited by 52 publications

(68 citation statements)

References 49 publications

(78 reference statements)

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“…Our results show that both culture systems preserve an unaltered cobblestone-shaped epicardial layer and sustain the overall slice viability and metabolic rate, comparable to previously reported myocardial slices from large mammals (30,36). Notably, the more stable environment provided by the dynamic culture system promote proliferation of epicardial cells.…”

Section: Discussionsupporting

confidence: 86%

Epicardial slices: a 3D organotypic model for the study of epicardial activation and differentiation

Maselli

Matos

Johnson

et al. 2020

Preprint

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The epicardium constitutes an untapped reservoir for cardiac regeneration. Upon myocardial injury, the adult epicardium re-activates the embryonic program, leading to epithelial-to-mesenchymal transition, migration and differentiation. Despite some successes in harnessing the epicardial therapeutic potential by thymosin β4 (Tβ4) pre-treatment, further translational advancements are hampered by the paucity of representative experimental models. Here we apply innovative protocols to obtain living 3D organotypic slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve the in vivo architecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon Tβ4 treatment of the slices, the epicardial cells become activated upregulating embryonic and EMT genes and invading the myocardium where they differentiate towards the mesenchymal lineage. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering a new tool to explore ex vivo the complex 3D interactions occurring within the native heart environment.

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Section: Discussionsupporting

confidence: 86%

Epicardial slices: a 3D organotypic model for the study of epicardial activation and differentiation

Maselli

Matos

Johnson

et al. 2020

Preprint

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“…In our lab we have pioneered the development of a novel in vitro cardiac model known as myocardial slices (Perbellini et al, 2017;Watson et al, 2017Watson et al, , 2019. Myocardial slices are living organotypic preparations that can be prepared from mammalian hearts including human biopsies (Watson et al, 2017).…”

Section: Experimental Models To Study Load-induced Remodelingmentioning

confidence: 99%

Heart Plasticity in Response to Pressure- and Volume-Overload: A Review of Findings in Compensated and Decompensated Phenotypes

Pitoulis

Terracciano

2020

Front. Physiol.

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The adult human heart has an exceptional ability to alter its phenotype to adapt to changes in environmental demand. This response involves metabolic, mechanical, electrical, and structural alterations, and is known as cardiac plasticity. Understanding the drivers of cardiac plasticity is essential for development of therapeutic agents. This is particularly important in contemporary cardiology, which uses treatments with peripheral effects (e.g., on kidneys, adrenal glands). This review focuses on the effects of different hemodynamic loads on myocardial phenotype. We examine mechanical scenarios of pressure-and volume overload, from the initial insult, to compensated, and ultimately decompensated stage. We discuss how different hemodynamic conditions occur and are underlined by distinct phenotypic and molecular changes. We complete the review by exploring how current basic cardiac research should leverage available cardiac models to study mechanical load in its different presentations.

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“…These allow investigators to prescribe the mechanical environment of cultured cells (Rosales and Kristi, 2016;Li et al, 2018). Alternatively, naturally occurring substrates like decellularized tissue (Ott et al, 2008) or living cardiac tissue slices (Perbellini et al, 2018) have been used to provide cells with near-physiological growth substrates, but these are more complex and less reproducible models. Substrates that more closely mimic in vivo conditions are essential as, while the overall stiffness of fibrotic tissue is raised when ECM production overcomes degradation (Levental et al, 2010), the stiffness distribution is highly heterogeneous.…”

Section: Introductionmentioning

confidence: 99%