Advances in the Generation of Constructed Cardiac Tissue Derived from Induced Pluripotent Stem Cells for Disease Modeling and Therapeutic Discovery

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 250 - 250

Published: Jan. 29, 2024

The human heart lacks significant regenerative capacity; thus, the solution to failure (HF) remains organ donation, requiring surgery and immunosuppression. demand for constructed cardiac tissues (CCTs) model treat disease continues grow. Recent advances in induced pluripotent stem cell (iPSC) manipulation, CRISPR gene editing, 3D tissue culture have enabled a boom iPSC-derived CCTs (iPSC-CCTs) with diverse types architecture. Compared 2D-cultured cells, iPSC-CCTs better recapitulate biology, demonstrating potential advance modeling, drug discovery, medicine, though could benefit from methods faithfully mimic physiology electrophysiology. Here, we summarize future developments vascularization, immunization, maturation of study therapy.

Language: Английский

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Advances in induced pluripotent stem cell‐derived cardiac myocytes: technological breakthroughs, key discoveries and new applications

The Journal of Physiology, Journal Year: 2024, Volume and Issue: 602(16), P. 3871 - 3892

Published: July 20, 2024

Abstract A transformation is underway in precision and patient‐specific medicine. Rapid progress has been enabled by multiple new technologies including induced pluripotent stem cell‐derived cardiac myocytes (iPSC‐CMs). Here, we delve into these advancements their future promise, focusing on the efficiency of reprogramming techniques, fidelity differentiation lineage, functional characterization resulting myocytes, many applications silico models to understand general mechanisms controlling excitation–contraction coupling health disease. Furthermore, explore current potential iPSC‐CMs both research clinical settings, underscoring far‐reaching implications this rapidly evolving field. image

Language: Английский

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Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 12, 2024

Ion channels and cytoskeletal proteins in the cardiac dyad play a critical role maintaining excitation-contraction (E-C) coupling provide homeostasis. Functional changes these proteins, whether induced by genetic, epigenetic, metabolic, therapeutic, or environmental factors, can disrupt normal electrophysiology, leading to abnormal E-C arrhythmias. Animal models heterologous cell cultures platforms elucidate pathogenesis of arrhythmias for basic research; however, traditional systems do not truly reflect human electro-pathophysiology. Notably, patients with same genetic variants inherited channelopathies (ICC) often exhibit incomplete penetrance variable expressivity which underscores need establish patient-specific disease comprehend mechanistic pathways determine personalized therapies. Patient-specific pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) inherit background patient electrophysiological characteristics native cardiomyocytes. Thus, iPSC-CMs an innovative translational pivotal platform modeling therapeutic screening. In this review, we will examine how historically evolved model arrhythmia syndromes dish, their utility understanding specific ion functional causing We also CRISPR/Cas9 have enabled establishment patient-independent variant-induced iPSC-CMs-based models. Next, limitations using respect

Language: Английский

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Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 28, 2025

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs effective treatments systemic diseases. While animal models have traditionally been pivotal in studying interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing vitro models. Beyond conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids emerged a substantial advancement, capable of replicating essential structural functional attributes internal organs vitro. This breakthrough has spurred development multilineage organoids, assembloids, organoids-on-a-chip technologies, which allow enhanced physiological relevance. These technologies shown great potential mimicking coordinated organogenesis, exploring disease pathogenesis, facilitating drug discovery. As central system, heart serves focal point an extensively studied network interactions. review focuses on advancements challenges organs, presenting comprehensive exploration this cutting-edge approach research.

Language: Английский

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Matured hiPSC-derived cardiomyocytes possess dematuration plasticity

Journal of Molecular and Cellular Cardiology Plus, Journal Year: 2025, Volume and Issue: unknown, P. 100295 - 100295

Published: March 1, 2025

Human induced Pluripotent Stem Cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used to identify potential factors capable of inducing endogenous cardiomyocyte proliferation regenerate the injured heart. L-type calcium channel blockers have previously been identified as a class matured hiPSC-CMs proliferate. However, mechanism by which promote hiPSC-CM remains unclear. Here we provide evidence that possess plasticity undergo dematuration in response certain pharmacological compounds. Consistent with primary maturation during perinatal development, found centrosome disassembly occurs plate-based, temporal, maturation. A small molecule screen nitrendipine, an blocker, and 1-NA-PP1, Src kinase inhibitor, reassembly subpopulation hiPSC-CMs. Furthermore, centrosome-positive were more likely exhibit cell cycle activity than centrosome-negative In contrast, neither nitrendipine or 1-NA-PP1 reassembly, activity, neonatal rat ventricular myocytes (NRVMs). Differential bulk transcriptome analysis indicated hiPSC-CMs, but not NRVMs, treated dematuration. ScRNA supported either Collectively, our results indicate compounds such Src-kinase inhibitors. This study shows once mature, may maintain their maturity under experimental conditions implications for systems where state is relevant.

Language: Английский

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Biocompatibility Assessment of an Injectable Carbon Nanotube-Functionalized Reverse Thermal Gel for Cardiac Tissue Engineering Applications

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Heart failure (HF) is a major contributor to the global burden of cardiovascular disease. Current treatments for HF do not regenerate or restore cardiac muscle function, leaving transplantation as only definitive treatment end-stage HF. Subsequently, there tremendous need alternative well methods effectively and selectively deliver those therapies heart. We have engineered an injectable reverse thermal gel (RTG) functionalized with carbon nanotubes (CNTs) create thermoresponsive conductive hydrogel RTG-CNT. The RTG-CNT transitions from liquid solution gel-based matrix upon reaching body temperature, unique quality that allows rapid injection polymeric followed by localization in situ. Previously, we demonstrated potential use tissue engineering applications using three-dimensional (3D) cocultures primary cells. Here, performed preclinical study assess biocompatibility our vivo intracardial mouse model vitro 3D cultures human-induced pluripotent stem cell-derived cardiomyocytes. In this report, present compelling results demonstrate its applications.

Language: Английский

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Polyploidy-mediated resilience in hepatic aging: molecular mechanisms and functional implication

Egyptian Liver Journal, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 12, 2024

Abstract Background Polyploidization, a process where cells acquire additional chromosome sets, is unique characteristic of hepatocytes. This has been increasingly recognized as an adaptive mechanism for maintaining liver function during aging, period characterized by cellular senescence, DNA damage, and metabolic dysregulation. Purpose review explores the molecular mechanisms underlying hepatocyte polyploidization its potential role in promoting resilience against aging-related decline function. We assess how polyploid hepatocytes contribute to genomic stability, stress resistance, adaptation, highlighting their relevance aging. Main body Hepatocyte occurs through such cytokinesis failure endoreplication, leading binuclear or mononuclear cells. Polyploid exhibit enhanced repair capacity, which helps mitigate accumulation age-related damage. The increased gene dosage facilitates better responses, particularly oxidative genotoxic insults. Metabolic adaptations, including xenobiotic metabolism lipid regulation, further support liver’s ability maintain homeostasis Additionally, demonstrate altered epigenetic landscapes proteostasis mechanisms, contributing improved reduced susceptibility senescence. These adaptations collectively enhance structural challenges. Conclusion represents critical protective that safeguard instability, dysfunction, stress. Understanding pathways driving could pave way novel therapeutic strategies combat disorders health span. Graphical

Language: Английский

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The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish

Medical Review, Journal Year: 2024, Volume and Issue: 4(1), P. 68 - 85

Published: Feb. 1, 2024

Cardiovascular research has heavily relied on studies using patient samples and animal models. However, often miss the data from crucial early stage of cardiovascular diseases, as obtaining primary tissues at this is impracticable. Transgenic models can offer some insights into disease mechanisms, although they usually do not fully recapitulate phenotype diseases their progression. In recent years, a promising breakthrough emerged in form

Language: Английский

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Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7971 - 7971

Published: July 21, 2024

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype lack of high-throughput analytical methodology. In this study, we developed testing platform utilizing hPSC-CMs to assess the cardiotoxicity effectiveness drugs. Following optimized differentiation maturation protocol, exhibited mature CM morphology, phenotype, functionality, making them suitable applications. We monitored intracellular calcium dynamics using imaging techniques measure spontaneous oscillations in presence or absence test compounds. For test, were treated with various compounds, flux was measured evaluate effects on dynamics. found that cardiotoxic drugs withdrawn due adverse reactions, including encainide, mibefradil, cetirizine, toxicity but not HEK293-hERG cells. Additionally, exposed ATX-II, sodium current inducer mimicking long QT syndrome type 3, followed exposure The observed changes following demonstrated utility versatile model system assessing both efficacy. Overall, our findings highlight potential advancing discovery development, which offer physiologically relevant preclinical screening novel therapeutics.

Language: Английский

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Injection of IK1 through dynamic clamp can make all the difference in patch-clamp studies on hiPSC-derived cardiomyocytes

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 12, 2023

Human-induced stem cell-derived cardiomyocytes (hiPSC-CMs) are a valuable tool for studying development, pharmacology, and (inherited) arrhythmias. Unfortunately, hiPSC-CMs depolarized spontaneously active, even the working cardiomyocyte subtypes such as atrial- ventricular-like hiPSC-CMs, in contrast to situation atria ventricles of adult human hearts. Great efforts have been made, using many different strategies, generate more mature, quiescent with close-to-physiological resting membrane potentials, but despite promising results, it is still difficult obtain properties. The dynamic clamp technique allows inject current characteristics inward rectifier potassium (IK1), computed real time according actual potential, into patch-clamped during action potential measurements. This results potential. As result, measurements can be performed normal ion channel availability, which particularly important physiological functioning cardiac SCN5A-encoded fast sodium (INa). We vitro silico experiments assess beneficial effects dissecting functional consequences SCN5A-1795insD+/- mutation. In two separate sets patch-clamp on control mutations ACADVL GNB5, we assessed value detecting delayed afterdepolarizations investigating factors that modulate conclude has highly all aforementioned settings should widely used studies while waiting ultimate fully mature hiPSC-CMs.

Language: Английский

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