Generation of human vascularized and chambered cardiac organoids for cardiac disease modelling and drug evaluation

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(8)

Published: March 7, 2024

Abstract Human induced pluripotent stem cell (hiPSC)‐derived cardiac organoids (COs) have shown great potential in modelling human heart development and cardiovascular diseases, a leading cause of global death. However, several limitations such as low reproducibility, limited vascularization difficulty formation chamber were yet to be overcome. We established new method for robust generation COs, via combination methodologies hiPSC‐derived vascular spheres directly differentiated cardiomyocytes from hiPSCs, investigated the application COs injury drug evaluation. The we built displayed vascularized chamber‐like structure, hence named vaschamcardioids (vcCOs). These vcCOs exhibited approximately 90% spontaneous beating ratio. Single‐cell transcriptomics identified total six types vcCOs, including cardiomyocytes, precursor cells, endothelial fibroblasts, etc. successfully recaptured processes fibrosis vivo on showed that FDA‐approved medication captopril significantly attenuated injury‐induced functional disorders. In addition, an obvious toxicity reaction doxorubicin dose‐dependent manner. developed three‐step complex our data suggested might become useful model understanding pathophysiological mechanisms developing intervention strategies screening drugs.

Language: Английский

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The Role of Stem Cells in the Treatment of Cardiovascular Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3901 - 3901

Published: March 31, 2024

Cardiovascular diseases (CVDs) are the leading cause of death and include several vascular cardiac disorders, such as atherosclerosis, coronary artery disease, cardiomyopathies, heart failure. Multiple treatment strategies exist for CVDs, but there is a need regenerative damaged heart. Stem cells broad variety with great differentiation potential that have immunomodulatory properties. studies evaluated efficacy stem in mesenchymal induced pluripotent cell-derived cardiomyocytes. These demonstrated can improve left ventricle ejection fraction, reduce fibrosis, decrease infarct size. Other investigated methods to survival, engraftment, functionality CVDs. The aim present review summarize current evidence on role how their efficacy.

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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Dissecting endothelial cell heterogeneity with new tools

Cell Regeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 23, 2025

Abstract The formation of a blood vessel network is crucial for organ development and regeneration. Over the past three decades, central molecular mechanisms governing growth have been extensively studied. Recent evidence indicates that vascular endothelial cells—the specialized cells lining inner surface vessels—exhibit significant heterogeneity to meet specific needs different organs. This review focuses on current understanding cell heterogeneity, which includes both intra-organ inter-organ heterogeneity. Intra-organ encompasses arterio-venous tip-stalk specialization, while refers organ-specific transcriptomic profiles functions. Advances in single-cell RNA sequencing (scRNA-seq) enabled identification new subpopulations comparison gene expression patterns across subsets cells. Integrating scRNA-seq with other high-throughput technologies promises deepen our at epigenetic level spatially resolved context. To further explore human organoids offer powerful tools studying function three-dimensional culture systems investigating endothelial-tissue interactions using Developing presents unique opportunities unravel its implications disease. Emerging technologies, such as organoids, are poised transform pave way innovative therapeutic strategies address diseases. Graphical

Language: Английский

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Progress of organoid platform in cardiovascular research

Bioactive Materials, Journal Year: 2024, Volume and Issue: 40, P. 88 - 103

Published: June 9, 2024

Language: Английский

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Cell-cell interactions in the heart: advanced cardiac models and omics technologies

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 12, 2024

A healthy heart comprises various cell types, including cardiomyocytes, endothelial cells, fibroblasts, immune and among others, which work together to maintain optimal cardiac function. These cells engage in complex communication networks, known as cell-cell interactions (CCIs), are essential for homeostasis, structure, efficient However, the context of diseases, undergoes damage, leading alterations cellular composition. Such pathological conditions trigger significant changes CCIs, causing rearrangement transition between types. Studying these can provide valuable insights into biology disease mechanisms, enabling development new therapeutic strategies. While organoids advanced 3D co-culture technologies has revolutionized vitro studies recent advancements single-cell spatial multi-omics researchers with powerful convenient tools investigate CCIs at unprecedented resolution. This article provides a concise overview observed both normal injured heart, an emphasis on cutting-edge methods used study interactions. It highlights such systems, omics technologies, that have enhanced understanding CCIs. Additionally, it summarizes practical applications CCI research advancing cardiovascular therapies, offering potential solutions treating by targeting intercellular communication.

Language: Английский

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Establishment of nasal and olfactory epithelium organoids for unveiling mechanism of tissue regeneration and pathogenesis of nasal diseases

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Jan. 3, 2025

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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Biomimetic Approaches in the Development of Optimised 3D Culture Environments for Drug Discovery in Cardiac Disease

Biomimetics, Journal Year: 2025, Volume and Issue: 10(4), P. 204 - 204

Published: March 26, 2025

Cardiovascular disease remains the leading cause of death worldwide, yet despite massive investment in drug discovery, progress cardiovascular drugs from lab to clinic slow. It is a complex, costly pathway discovery and failure becomes more expensive as progresses along this pathway. The focus has begun shift optimisation vitro culture methodologies, not only because these must be undertaken are earlier on pathway, but also principles 3Rs have become embedded national international legislation regulation. Numerous studies shown myocyte cell behaviour much physiologically relevant 3D compared 2D culture, highlighting advantages using 3D-based models, whether microfluidic or otherwise, for preclinical screening. This review aims provide an overview challenges limitations traditional routes, successes field models discovery. focuses particular role biomimicry can play, around implementation within commercial

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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