Development of appropriate fatty acid formulations to raise the contractility of constructed myocardial tissues

Yoshida, Azumi; Sekine, Waki; Homma, Jun; Sekine, Hidekazu; Itoyama, Yu Yamasaki; Sasaki, Daisuke; Matsuura, Kiyotaka; Kobayashi, Eiji; Shimizu, Tatsuya

doi:10.1016/j.reth.2022.09.006

Cited by 7 publications

(2 citation statements)

References 43 publications

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“…5) increase cardiomyocyte size, anisotropy, and sarcomere length as well as promoting T-tubule formation and electrophysiological maturation [24][25][26] . Similarly, cardiomyocyte maturation is reported to be improved by the addition of fatty acids to the media 27,28 . It would be interesting to determine the effect of Sfrp2 in these systems.…”

Section: Discussionmentioning

confidence: 96%

Novel method of differentiating human induced pluripotent stem cells to mature cardiomyocytes via Sfrp2

Hsueh

Pratt

Dzau

et al. 2023

Sci Rep

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Current methods to generate cardiomyocytes from induced pluripotent stem cells (iPSc) utilize broad-spectrum pharmacological inhibitors. These methods give rise to cardiomyocytes which are typically immature. Since we have recently demonstrated that cardiomyogenesis in vitro and in vivo requires Sfrp2, we asked if Sfrp2 would drive differentiation of human iPSc into cardiomyocytes. Indeed, we found that Sfrp2 induced robust cardiac differentiation. Importantly, replacement of broad spectrum pharmacological inhibitors with Sfrp2 gave rise to mature cardiomyocytes as evidenced by their sarcomere structure, electrophysiological profiles, and ability to form gap junctions.

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Section: Discussionmentioning

confidence: 96%

Novel method of differentiating human induced pluripotent stem cells to mature cardiomyocytes via Sfrp2

Hsueh

Pratt

Dzau

et al. 2023

Sci Rep

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“…This dyn-EHT application of preload has also been shown to be critical in driving the emergence of disease phenotypes linked to genetic mutations, such as in arrhythmogenic cardiomyopathy and dilated cardiomyopathy 29,55 . Other factors to implement that can drive cardiac tissue maturation include electrical stimulation during culture 56 , biochemical stimulation such as triiodo-L-thyronine (T3) hormone 57 , and fatty acid metabolism [58][59][60][61] . Additional functional readouts are also needed, including contractile force and voltage mapping to quantify the action potential.…”

Section: Discussionmentioning

confidence: 99%

FRESH™ 3D Bioprinted Cardiac Tissue, a Bioengineered Platform for in vitro Toxicology and Pharmacology

Finkel¹,

Sweet²,

Locke³

et al. 2023

Preprint

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There is critical need for a predictive model of human cardiac physiology in the drug development process for assessment of compound toxicology and pharmacology. In vitro two-dimensional monolayer culture of cardiomyocytes provides biochemical and cellular readouts, and in vivo small and large animal models provide information on systemic cardiovascular response. However, there remains a significant gap in these models due to an incomplete recapitulation of adult human cardiovascular physiology, which results in more difficult safety interpretations. Recent efforts in developing in vitro models from engineered heart tissues have demonstrated potential for bridging this gap using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in a three-dimensional tissue structure. Here we advance this paradigm by implementing FRESH 3D bioprinting to build human cardiac tissues in a medium throughput, well-plate format with controlled tissue architecture, tailored cellular composition, and native-like physiological function, specifically in its adrenergic agonist drug response. To do this, we combined hiPSC-CMs, endothelial cells and fibroblasts in a cellular bioink and FRESH 3D bioprinted this mixture in the format of a thin tissue strip stabilized on a tissue fixture. Our results confirmed that FRESH 3D bioprinted cardiac tissues could be fabricated directly in a 24-well plate format, were composed of dense and highly aligned hiPSC-CMs at >600 million cells/mL, and within 14 days demonstrated reproducible calcium transients and fast conduction velocity of ~25 cm/s. Interrogation of these cardiac tissues with the β-adrenergic receptor agonist isoproterenol showed native-like positive chronotropic and inotropic responses, a combination of responses that is not typically observed in 2D monolayer models or standard 3D engineered heart tissue approaches. These results confirm that FRESH 3D bioprinted cardiac tissues represents a novel in vitro platform that enables early in vitro pharmacology and toxicology screening.

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Multifactorial approaches to enhance maturation of human iPSC-derived cardiomyocytes

Kistamás

Müller

Muenthaisong

et al. 2023

Journal of Molecular Liquids

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Development of appropriate fatty acid formulations to raise the contractility of constructed myocardial tissues

Cited by 7 publications

References 43 publications

Novel method of differentiating human induced pluripotent stem cells to mature cardiomyocytes via Sfrp2

Novel method of differentiating human induced pluripotent stem cells to mature cardiomyocytes via Sfrp2

FRESH™ 3D Bioprinted Cardiac Tissue, a Bioengineered Platform for in vitro Toxicology and Pharmacology

Multifactorial approaches to enhance maturation of human iPSC-derived cardiomyocytes

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