Fatty acid-based monolayer culture to promote in vitro neonatal rat cardiomyocyte maturation

Isu, Giuseppe; Diaz, Diana Robles; Grussenmeyer, Thomas; Gaudiello, Emanuele; Eckstein, Friedrich S.; Brink, Marijke; Marsano, Anna

doi:10.1016/j.bbamcr.2019.118561

Cited by 8 publications

(7 citation statements)

References 28 publications

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“…Influencing metabolism in differentiating CMs from iPSCs might be an inexpensive and valuable solution to improve cell maturity [37,39,40,143,174,216,224]. Furthermore, atria and ventricles exhibit different metabolic enzyme expressions and different amino acid metabolism, with the ventricle utilizing lower levels of aspartate, glycine, and proline [180,181].…”

Section: Discussionmentioning

confidence: 99%

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Bizy

Klos

2020

Animals

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Heart failure (HF) is a common disease in which the heart cannot meet the metabolic demands of the body. It mostly occurs in individuals 65 years or older. Cardiac transplantation is the best option for patients with advanced HF. High numbers of patient-specific cardiac myocytes (CMs) can be generated from induced pluripotent stem cells (iPSCs) and can possibly be used to treat HF. While some studies found iPSC-CMS can couple efficiently to the damaged heart and restore cardiac contractility, almost all found iPSC-CM transplantation is arrhythmogenic, thus hampering the use of iPSC-CMs for cardiac regeneration. Studies show that iPSC-CM cultures are highly heterogeneous containing atrial-, ventricular- and nodal-like CMs. Furthermore, they have an immature phenotype, resembling more fetal than adult CMs. There is an urgent need to overcome these issues. To this end, a novel and interesting avenue to increase CM maturation consists of modulating their metabolism. Combined with careful engineering and animal models of HF, iPSC-CMs can be assessed for their potential for cardiac regeneration and a cure for HF.

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Section: Discussionmentioning

confidence: 99%

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Bizy

Klos

2020

Animals

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“…All the acquired images were then processed with the threshold technique “Intermodes” to segment Cx-43-positive entities and the threshold technique ‘‘Li dark method’’ to segment Sarcomeric α-actinin-positive entities. With these techniques, the percentage of area positive for Cx-43 and the percentage of area positive for Sarcomeric α-actinin were quantified ( Navaei et al, 2017 ; Lemme et al, 2018 ; Isu et al, 2020 ; Pisanu et al, 2022 ). Finally, to understand the portion of CMs which underwent a good maturation in terms of sarcomeric organization, the percentage of CMs with sarcomeric organization with respect to the total number of CMs was quantified ( Mytsyk et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Versatile electrical stimulator for cardiac tissue engineering—Investigation of charge-balanced monophasic and biphasic electrical stimulations

Gabetti

Sileo²,

Montrone³

et al. 2023

Front. Bioeng. Biotechnol.

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The application of biomimetic physical stimuli replicating the in vivo dynamic microenvironment is crucial for the in vitro development of functional cardiac tissues. In particular, pulsed electrical stimulation (ES) has been shown to improve the functional properties of in vitro cultured cardiomyocytes. However, commercially available electrical stimulators are expensive and cumbersome devices while customized solutions often allow limited parameter tunability, constraining the investigation of different ES protocols. The goal of this study was to develop a versatile compact electrical stimulator (ELETTRA) for biomimetic cardiac tissue engineering approaches, designed for delivering controlled parallelizable ES at a competitive cost. ELETTRA is based on an open-source micro-controller running custom software and is combinable with different cell/tissue culture set-ups, allowing simultaneously testing different ES patterns on multiple samples. In particular, customized culture chambers were appositely designed and manufactured for investigating the influence of monophasic and biphasic pulsed ES on cardiac cell monolayers. Finite element analysis was performed for characterizing the spatial distributions of the electrical field and the current density within the culture chamber. Performance tests confirmed the accuracy, compliance, and reliability of the ES parameters delivered by ELETTRA. Biological tests were performed on neonatal rat cardiac cells, electrically stimulated for 4 days, by comparing, for the first time, the monophasic waveform (electric field = 5 V/cm) to biphasic waveforms by matching either the absolute value of the electric field variation (biphasic ES at ±2.5 V/cm) or the total delivered charge (biphasic ES at ±5 V/cm). Findings suggested that monophasic ES at 5 V/cm and, particularly, charge-balanced biphasic ES at ±5 V/cm were effective in enhancing electrical functionality of stimulated cardiac cells and in promoting synchronous contraction.

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“…Microfluidics enhances muscle-tissue development and maturation by easily implementing coculture systems between muscle cells and other cell types. For example, the presence of fibroblasts can promote the differentiation of myogenic cells, while the presence of adipocytes can alter the availability of metabolites and affect the metabolic processes in muscle cells ( 95 ). Endothelial cells and neurons can generate integrated networks essential for the functioning of tissue; these networks of endothelial cells and neurons perfuse tissue (vascularization) or convey signals (innervation), respectively.…”

Section: Microfluidics For Bioactuatorsmentioning

confidence: 99%

Will microfluidics enable functionally integrated biohybrid robots?

Filippi

Yaşa

Kamm

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The next robotics frontier will be led by biohybrids. Capable biohybrid robots require microfluidics to sustain, improve, and scale the architectural complexity of their core ingredient: biological tissues. Advances in microfluidics have already revolutionized disease modeling and drug development, and are positioned to impact regenerative medicine but have yet to apply to biohybrids. Fusing microfluidics with living materials will improve tissue perfusion and maturation, and enable precise patterning of sensing, processing, and control elements. This perspective suggests future developments in advanced biohybrids.

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Fatty acid-based monolayer culture to promote in vitro neonatal rat cardiomyocyte maturation

Cited by 8 publications

References 28 publications

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Versatile electrical stimulator for cardiac tissue engineering—Investigation of charge-balanced monophasic and biphasic electrical stimulations

Will microfluidics enable functionally integrated biohybrid robots?

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