Vascular cells improve functionality of human cardiac organoids

Cell Reports, Journal Year: 2023, Volume and Issue: 42(5), P. 112322 - 112322

Published: April 26, 2023

Crosstalk between cardiac cells is critical for heart performance. Here we show that vascular within human organoids (hCOs) enhance their maturation, force of contraction, and utility in disease modeling. Herein optimize our protocol to generate populations addition epicardial, fibroblast, cardiomyocyte self-organize into in-vivo-like structures hCOs. We identify mechanisms communication endothelial cells, pericytes, fibroblasts, cardiomyocytes ultimately contribute organoid maturation. In particular, (1) endothelial-derived LAMA5 regulates expression mature sarcomeric proteins contractility, (2) paracrine platelet-derived growth factor receptor β (PDGFRβ) signaling from upregulates matrix deposition augment hCO contractile force. Finally, demonstrate determine the magnitude diastolic dysfunction caused by inflammatory factors a role endothelin driving dysfunction. Together this study highlights importance models.

Language: Английский

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Low-dose of polystyrene microplastics induce cardiotoxicity in mice and human-originated cardiac organoids

Environment International, Journal Year: 2023, Volume and Issue: 179, P. 108171 - 108171

Published: Aug. 25, 2023

Microplastic particles (MP) are prevalent in both industrial production and the natural environment, posing a significant concern for human health. Daily diet, air inhalation, skin contact major routines of MP intake human. The main injury target systems MPs include digestive system, respiratory cardiovascular system. However, study on MPs' adverse effects heart is less than other organs. Previous vivo studies have demonstrated that can induce injuries, including abnormal rate, apoptosis cardiomyocytes, mitochondrial membrane potential change, fibrin overexpression. To address animal welfare concerns overcome inter-species variations, this employed pluripotent stem cell-derived vitro three-dimensional cardiac organoid (CO) model to investigate heart. distinct cavities COs allowed observation aggregation spatial distribution following polystyrene-MP (PS) exposure dynamic After various concentrations PS (0.025, 0.25 2.5 µg/mL, with lowest concentration equivalent internal levels), exhibited increased oxidative stress, inflammatory response, apoptosis, collagen accumulation. These findings were consistent observations, terms increases interventricular septal thickness. expression hypertrophic-related genes (MYH7B/ANP/BNP/COL1A1) changed noticeably cardiac-specific markers MYL2/MYL4/CX43 also markedly elevated. Our revealed could induced hypertrophy vitro, indicating may be an under-recognized risk factor

Language: Английский

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Organoids are not organs: Sources of variation and misinformation in organoid biology

Stem Cell Reports, Journal Year: 2023, Volume and Issue: 18(6), P. 1255 - 1270

Published: June 1, 2023

In the past decade, term organoid has moved from obscurity to common use describe a 3D in vitro cellular model of tissue that recapitulates structural and functional elements vivo organ it models. The is now applied structures formed as result two distinct processes: capacity for adult epithelial stem cells re-create niche ability direct differentiation pluripotent self-organizing multicellular organogenesis. While these fields rely upon different cell types recapitulate processes, both share challenges around robustness, accuracy, reproducibility. Critically, organoids are not organs. This commentary serves discuss challenges, how they impact genuine utility, shine light on need improve standards all approaches.

Language: Английский

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Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(12), P. 1787 - 1800

Published: April 3, 2023

Abstract The epicardium, the mesothelial envelope of vertebrate heart, is source multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids display retinoic acid-dependent morphological, molecular functional patterning epicardium myocardium typical left ventricular wall. By combining lineage tracing, single-cell transcriptomics chromatin accessibility profiling, describe specification differentiation process different in draw comparisons fetal at transcriptional morphological levels. We then use investigate cross-talk between types, gaining new insights into role IGF2/IGF1R NRP2 signaling cardiogenesis. Finally, show mimic multicellular pathogenesis congenital or stress-induced hypertrophy fibrotic remodeling. As such, offer a unique testing ground epicardial activity heart development, disease regeneration.

Language: Английский

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A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 12, 2023

Abstract Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart by mimicking aspects utero gestation (e.g., addition metabolic and hormonal factors) would lead to higher physiological anatomical relevance. find produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally morphologically age-matched embryonic hearts. also show they several cardiac development, including large atrial ventricular chambers, proepicardial formation, retinoic acid-mediated anterior-posterior patterning, the processes found post-heart tube stage primitive heart. Moreover, we provide proof-of-concept demonstration value system for disease modeling exploring effects ondansetron, a drug administered pregnant women associated with congenital defects. These findings constitute technical advance synthetic powerful tool modeling.

Language: Английский

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Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 22, 2024

Abstract Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of derived from pluripotent stem cells are often limited due to their immaturity lack functionality. Therefore, in this study, we establish a perfusable culture system based on vivo-like heart microenvironments improve tissue fabrication. The integrated platform microfluidic chip three-dimensional extracellular matrix enhances development structural functional maturation. These comprised cardiovascular lineage cells, cardiomyocytes fibroblasts induced as well vascular endothelial cells. resultant macroscale exhibit improved efficacy testing (small molecules with levels arrhythmia risk), modeling (Long QT Syndrome fibrosis), therapy (myocardial infarction treatment). our can serve highly effective tissue-engineering provide versatile applications.

Language: Английский

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Integrating organoids and organ-on-a-chip devices

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(7), P. 588 - 608

Published: July 2, 2024

Language: Английский

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Developing fibrin-based biomaterials/scaffolds in tissue engineering

Bioactive Materials, Journal Year: 2024, Volume and Issue: 40, P. 597 - 623

Published: Aug. 15, 2024

Tissue engineering technology has advanced rapidly in recent years, offering opportunities to construct biologically active tissues or organ substitutes repair even enhance the functions of diseased and organs. Tissue-engineered scaffolds rebuild extracellular microenvironment by mimicking matrix. Fibrin-based possess numerous advantages, including hemostasis, high biocompatibility, good degradability. Fibrin provide an initial matrix that facilitates cell migration, differentiation, proliferation, adhesion, also play a critical role cell-matrix interactions. are now widely recognized as key component tissue engineering, where they can facilitate defect repair. This review introduces properties fibrin, its composition, structure, biology. In addition, modification cross-linking modes fibrin discussed, along with various forms commonly used engineering. We describe biofunctionalization fibrin. provides detailed overview use applications skin, bone, nervous tissues, novel insights into future research directions for clinical treatment.

Language: Английский

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Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Feb. 12, 2024

Abstract Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor along considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as vitro cell cultures vivo animal models, demonstrate significant limitations that fall short satisfying the research requisites. Patient-derived organoids, which recapitulate structures, specific functions, molecular characteristics, genomics alterations expression profiles primary tumors. They have been efficaciously implemented illness portrayal, mechanism exploration, high-throughput drug screening assessment, discovery innovative therapeutic targets potential compounds, customized treatment regimen cancer In contrast conventional organoids offer an intuitive, dependable, efficient model by conserving phenotypic, genetic diversity, mutational attributes originating tumor. Nevertheless, organoid technology also confronts bottlenecks challenges, how comprehensively reflect microenvironment, angiogenesis, reduce costs, establish standardized construction processes while retaining reliability. This review extensively examines use techniques fundamental precision medicine. It emphasizes importance patient-derived biobanks development, screening, safety evaluation, personalized Additionally, it evaluates application experimental better understand mechanisms The intent this explicate significance present new avenues future research.

Language: Английский

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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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