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

Cell Proliferation, Год журнала: 2024, Номер 57(8)

Опубликована: Март 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.

Язык: Английский

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The Role of Stem Cells in the Treatment of Cardiovascular Diseases

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3901 - 3901

Опубликована: Март 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.

Язык: Английский

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Engineering Cardiology with Miniature Hearts

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101505 - 101505

Опубликована: Янв. 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.

Язык: Английский

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Dissecting endothelial cell heterogeneity with new tools

Cell Regeneration, Год журнала: 2025, Номер 14(1)

Опубликована: Март 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

Язык: Английский

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Progress of organoid platform in cardiovascular research

Bioactive Materials, Год журнала: 2024, Номер 40, С. 88 - 103

Опубликована: Июнь 9, 2024

Язык: Английский

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

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 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.

Язык: 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, Год журнала: 2025, Номер 82(1)

Опубликована: Янв. 3, 2025

Язык: 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), Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3016 - 3016

Опубликована: Март 26, 2025

The growing prevalence of diabetes highlights the urgent need to study diabetic cardiovascular complications, specifically cardiomyopathy, which is a diabetes-induced myocardial dysfunction independent hypertension or coronary artery disease. This review examines role mitochondrial in promoting cardiac and metabolic mechanisms such as hyperglycaemia-induced oxidative stress. Chronic hyperglycaemia insulin resistance can activate harmful pathways, including advanced glycation end-products (AGEs), protein kinase C (PKC) hexosamine signalling, uncontrolled reactive oxygen species (ROS) production mishandling Ca2+ transient. These processes lead cardiomyocyte apoptosis, fibrosis contractile dysfunction. Moreover, endoplasmic reticulum (ER) stress dysregulated RNA-binding proteins (RBPs) extracellular vesicles (EVs) contribute tissue damage, drives function towards heart failure (HF). Advanced patient-derived induced pluripotent stem cell (iPSC) organoids (iPS-COs) are transformative tools for modelling cardiomyopathy capturing human disease's genetic, epigenetic hallmarks. iPS-COs may facilitate precise examination molecular pathways therapeutic interventions. Future research directions encourage integration models with mechanistic techniques promote novel strategies.

Язык: Английский

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Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3038 - 3038

Опубликована: Март 26, 2025

Cardiovascular diseases (CVD), the leading cause of death worldwide, and their strong association with fibrosis highlight pressing need for innovative antifibrotic therapies. In vitro models have emerged as valuable tools replicating cardiac 'in a dish', facilitating study disease mechanisms serving platforms drug testing development. These in systems encompass 2D 3D models, each its own limitations advantages. offer high reproducibility, cost-effectiveness, high-throughput capabilities, but they oversimplify complex fibrotic environment. On other hand, provide greater biological relevance are more complex, harder to reproduce, less suited screening. The choice model depends on specific research question stage Despite significant progress, challenges remain, including integration immune cells optimizing scalability throughput highly biomimetic systems. Herein, we review recent focus shared characteristics remaining challenges, explore how organs could inspire novel approaches research, showcasing potential strategies that be adapted refine myocardial models.

Язык: Английский

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