Comparisons of wave dynamics in Hodgkin-Huxley and Markov-state formalisms for the sodium (Na) channel in some mathematical models for human cardiac tissue

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

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Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential

Cells ◽

10.3390/cells10061516 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1516

Author(s):

Daniel Gratz ◽

Alexander J Winkle ◽

Seth H Weinberg ◽

Thomas J Hund

Keyword(s):

Action Potential ◽

Mathematical Models ◽

Cardiac Myocyte ◽

Population Level ◽

Na Channel ◽

Model Parameters ◽

Healthy Population ◽

Experimental Measurements ◽

Voltage Gated ◽

Experimental Variability

The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.

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Comparative analysis of oncofetal fibronectin and tenascin-C expression in right atrial auricular and left ventricular human cardiac tissue from patients with coronary artery disease and aortic valve stenosis

Histochemistry and Cell Biology ◽

10.1007/s00418-011-0809-z ◽

2011 ◽

Vol 135 (5) ◽

pp. 427-441 ◽

Cited By ~ 10

Author(s):

Anja Baldinger ◽

Bernhard R. Brehm ◽

Petra Richter ◽

Torsten Bossert ◽

Katja Gruen ◽

...

Keyword(s):

Coronary Artery Disease ◽

Comparative Analysis ◽

Coronary Artery ◽

Aortic Valve ◽

Cardiac Tissue ◽

Left Ventricular ◽

Right Atrial ◽

Oncofetal Fibronectin ◽

Artery Disease ◽

Human Cardiac Tissue

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Abstract 020: Cell-sheet-based Bioengineered Human Cardiac Tissue Using Pluripotent Stem Cells For Heart Repair And Disease Models

Circulation Research ◽

10.1161/res.113.suppl_1.a020 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Katsuhisa Matsuura ◽

Tatsuya Shimizu ◽

Nobuhisa Hagiwara ◽

Teruo Okano

Keyword(s):

Cardiac Tissue ◽

Subcutaneous Tissue ◽

Cell Sheet ◽

Three Dimensional ◽

Embryoid Bodies ◽

Cardiac Differentiation ◽

Cardiac Cell ◽

Cell Sheets ◽

High Efficient ◽

Human Cardiac Tissue

We have developed an original scaffold-free tissue engineering approach, “cell sheet engineering”, and this technology has been already applied to regenerative medicine of various organs including heart. As the bioengineered three-dimensional cardiac tissue is expected to not only function for repairing the broad injured heart but also to be the practicable heart tissue models, we have developed the cell sheet-based perfusable bioengineered three-dimensional cardiac tissue. Recently we have also developed the unique suspension cultivation system for the high-efficient cardiac differentiation of human iPS cells. Fourteen-day culture with the serial treatments of suitable growth factors and a small compound in this stirring system with the suitable dissolved oxygen concentration produced robust embryoid bodies that showed the spontaneous beating and were mainly composed of cardiomyocytes (~80%). When these differentiated cells were cultured on temperature-responsive culture dishes after the enzymatic dissociation, the spontaneous and synchronous beating was observed accompanied with the intracellular calcium influx all over the area even after cell were detached from culture dishes as cell sheets by lowering the culture temperature. The cardiac cell sheets were mainly composed of cardiomyocytes (~80%) and partially mural cells (~20%). Furthermore, extracellular action potential propagation was observed between cell sheets when two cardiac cell sheets were partially overlaid, and this propagation was inhibited by the treatment with some anti-arrhythmic drugs. When the triple layered cardiac tissue was transplanted onto the subcutaneous tissue of nude rats, the spontaneous pulsation was observed over 2 months and engrafted cardiomyocytes were vascularized with the host tissue-derived endothelial cells. These findings suggest that cardiac cell sheets formed by hiPSC-derived cardiomyocytes might have sufficient properties for the creation of thickened cardiac tissue. Now we are developing the vascularized thickened human cardiac tissue by the repeated layering of cardiac cell sheets on the artificial vascular bed in vitro.

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