Applications of 3D organoids in toxicological studies: a comprehensive analysis based on bibliometrics and advances in toxicological mechanisms

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(8), P. 2309 - 2330

Published: May 28, 2024

Language: Английский

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Complex in vitro models positioned for impact to drug testing in pharma: a review

Biofabrication, Journal Year: 2024, Volume and Issue: 16(4), P. 042006 - 042006

Published: Aug. 27, 2024

Abstract Recent years have seen the creation and popularization of various complex in vitro models (CIVMs), such as organoids organs-on-chip, a technology with potential to reduce animal usage pharma while also enhancing our ability create safe efficacious drugs for patients. Public awareness CIVMs has increased, part, due recent passage FDA Modernization Act 2.0. This visibility is expected spur deeper investment adoption models. Thus, end-users model developers alike require framework both understand readiness current enter drug development process, assess upcoming same. review presents selection based on comparative -omics data (which we term model-omics), metrics qualification specific test assays that may support context-of-use (COU) assays. We surveyed existing healthy tissue ten development-critical organs body, provide evaluations suggestions improving model-omics COU each. In whole, this comes from perspective, seeks an evaluation where are poised maximum impact roadmap realizing potential.

Language: Английский

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Unveiling the Heart’s Hidden Enemy: Dynamic Insights into Polystyrene Nanoplastic-Induced Cardiotoxicity Based on Cardiac Organoid-on-a-Chip

ACS Nano, Journal Year: 2024, Volume and Issue: 18(45), P. 31569 - 31585

Published: Nov. 1, 2024

Exposure to micro- and nanoplastics (MNPs) has been implicated in potential cardiotoxicity. However, vitro models based on cardiomyocyte cell lines lack crucial cardiac characteristics, while interspecies differences animal compromise the reliability of conclusions. In addition, current research predominantly focused single-time point exposures MNPs, neglecting comparative analyses injury across early late stages. Moreover, there remains a large gap understanding susceptibility MNPs under pathological conditions. To address these limitations, this study integrated organoids (COs) organ-on-a-chip (OoC) technology develop organoid-on-a-chip (COoC), which was validated for cardiotoxicity evaluation through multiple dimensions. Based COoC, we conducted dynamic observation damage caused by short- long-term exposure polystyrene (PS-NPs). Oxidative stress, inflammation, disruption calcium ion homeostasis, mitochondrial dysfunction were confirmed as mechanisms PS-NP-induced events stages, fibrosis emerged prominent feature Notably, low-dose exacerbated myocardial infarction symptoms states, despite no significant shown healthy models. conclusion, findings further deepened our cardiotoxic effects introduced promising platform assessing

Language: Английский

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Recreating coronary vascularization and sympathetic innervation of myocardium on a human pluripotent stem cell-derived heart organoid

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

SUMMARY Coronary vascularization and sympathetic innervation of the myocardium is a concomitant event during embryonic heart development both systems are crucial to ensure normal adult function. Here we describe self-organized hiPSC-derived organoid that recreates coronary vascular plexus neuronal network ventricle myocardium, with physiologically relevant in-vivo-like structural organization Through modulation PDGF-β VEGF signalling pathways, attained incorporates 1) an external epicardial layer (mesothelium) DACH1, NR2F2 WT1 positive cells, 2) sub-epicardial space from where functional primary CD31 + /DACH1 cells emerge, 3) compact myocardial region adjacent epicardium, enriched in proliferative cardiomyocytes ECM deposition, 4) controls contraction. Therefore, human described herein, unique model study new regenerative medicine-based approaches restore promote re-vascularization after ischemic events perform developmental cardiotoxicity studies.

Language: Английский

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Advances in cardiac organoid research: implications for cardiovascular disease treatment

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 18, 2025

Globally, cardiovascular diseases remain among the leading causes of mortality, highlighting urgent need for innovative research models. Consequently, development accurate models that simulate cardiac function holds significant scientific and clinical value both disease therapeutic interventions. Cardiac organoids, which are three-dimensional structures derived from induced differentiation stem cells, particularly promising. These organoids not only replicate autonomous beating essential electrophysiological properties heart but also widely employed in studies related to diseases, drug efficacy testing, regenerative medicine. This review comprehensively surveys various fabrication techniques used create their diverse applications modeling a range diseases. We emphasize role advanced technologies enhancing maturation functionality ensuring these closely resemble native tissue. Furthermore, we discuss monitoring evaluation parameters critical assessing performance considering complex interactions within multi-organ systems. approach is vital precision efficiency development, allowing more effective strategies. Ultimately, this aims provide thorough perspective on fundamental treatment offering insights could pave way future advancements understanding addressing prevalent health challenges.

Language: Английский

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LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The genetic variants of LMNA cause an array diseases that often affect the heart. LMNA-related cardiomyopathy exhibits high-penetrance and early-onset phenotypes lead to late-stage heart failure or lethal arrhythmia. As a subtype dilated arrhythmogenic cardiomyopathy, cardiac dysfunction is resistant existing therapeutic strategies, leaving major unmet clinical need in management. Here we comprehensively summarize current knowledge about basis, disease models pathological mechanisms cardiomyopathy. Recent translational studies were highlighted indicate new modalities such as gene supplementation, silencing genome editing therapy, which offer potential opportunities overcome difficulties development specific drugs for this disease. involves many diverse preclude small-molecule target only small fraction mechanisms. Agreeing notion, first-in-human trial recently reported futility. By contrast, therapy offers hope directly intervene demonstrates tremendous breakthrough Concepts review are also applicable other lack effective therapeutics.

Language: Английский

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Engineering Cardiology with Miniature Hearts

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101505 - 101505

Published: Jan. 22, 2025

Cardiac organoids offer sophisticated 3D structures that emulate key aspects of human heart development and function. This review traces the evolution cardiac organoid technology, from early stem cell differentiation protocols to advanced bioengineering approaches. We discuss methodologies for creating organoids, including self-organization techniques, biomaterial-based scaffolds, bioprinting, organ-on-chip platforms, which have significantly enhanced structural complexity physiological relevance in vitro models. examine their applications fundamental research medical innovations, highlighting potential transform our understanding biology pathology. The integration multiple types, vascularization strategies, maturation has led more faithful representations adult heart. However, challenges remain achieving full functional maturity scalability. critically assess current limitations outline future directions advancing technology. By providing a comprehensive analysis field, this aims catalyze further innovation tissue engineering facilitate its translation clinical applications.

Language: Английский

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3D Spatiotemporal Activation Mapping of Cardiac Organoids Using Conformal Shell Microelectrode Arrays (MEAs)

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Cardiac organoids have emerged as transformative models for investigating cardiogenesis and cardiac diseases. While traditional 2D microelectrode arrays (MEAs) been used to assess the functionality of organoids, they are limited electrophysiological measurements from a single plane do not capture 3D propagation electrical signals. Here, we present programmable, shape-adaptive shell MEA designed map activity across entire surface organoids. These MEAs fabricated on-chip, with tunable dimensions electrode layout, enabling precise encapsulation spherical Using MEAs, generated isochrone maps conduction velocity vectors, revealing speed trajectory signal in spontaneously beating The optical transparency allowed simultaneous calcium imaging, validating pattern. To demonstrate their utility cardiotoxicity screening, monitored changes treated isoproterenol E-4031 over nine days. We anticipate that combined spatiotemporal mapping, can significantly advance development spatially organized structural disease models, high-throughput drug screening platforms.

Language: Английский

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Low dose of micro-/nano-plastics mixture induced cardiac hypertrophy and reductive stress: the liver-heart crosstalk and hepatic-cardiac organoids-on-a-chip

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 490, P. 137686 - 137686

Published: Feb. 20, 2025

Language: Английский

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Evolving from organoid to assembloid with enhanced cellular interactions

Cell organoid (Print), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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