Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 26, 2021

Abstract Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model accurately in vitro. Here we report a method generate developmentally relevant organoids self-assembly using pluripotent stem cells. Our procedure fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through three-step Wnt signaling modulation strategy chemical inhibitors growth factors. Heart comparable age-matched fetal cardiac tissues at transcriptomic, structural, cellular level. They develop sophisticated internal chambers well-organized multi-lineage cell types, recapitulate field formation atrioventricular specification, complex vasculature, exhibit robust functional activity. We also show that organoid platform can recreate metabolic associated congenital defects, as demonstrated an vitro pregestational diabetes-induced defects.

Language: Английский

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Vascular endothelial cell development and diversity

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(3), P. 197 - 210

Published: Oct. 5, 2022

Language: Английский

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Human organoids in basic research and clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 24, 2022

Abstract Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult (AdSCs) derived healthy individuals patients that recapitulate the cellular heterogeneity, structure, and functions of organs. The advent 3D organoid systems is now possible to allow remarkably detailed observation cell morphogens, maintenance differentiation resemble primary tissues, enhancing potential study both physiology developmental stage. As they similar their original organs carry genetic information, organoids patient hold great promise for biomedical research preclinical drug testing currently used personalized, regenerative medicine, gene repair transplantation therapy. In recent decades, researchers have succeeded generating various types mimicking vivo Herein, we provide an update on current technologies brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized multi-lineage organoids, discuss differences between PSC- AdSC-derived summarize applications cell-derived laboratory clinic, outline challenges application which would deepen understanding mechanisms development enhance further utility basic clinical studies.

Language: Английский

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Challenges and opportunities for the next generation of cardiovascular tissue engineering

Nature Methods, Journal Year: 2022, Volume and Issue: 19(9), P. 1064 - 1071

Published: Sept. 1, 2022

Language: Английский

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Organoids: The current status and biomedical applications

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 17, 2023

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that derived from cells with stem potential and can self-organize differentiate into 3D cell masses, recapitulating the morphology functions their in vivo counterparts. Organoid culture is an emerging technology, organoids various tissues, such as brain, lung, heart, liver, kidney, have been generated. Compared traditional bidimensional culture, organoid systems unique advantage conserving parental gene expression mutation characteristics, well long-term maintenance function biological characteristics vitro. All these features open up new opportunities for drug discovery, large-scale screening, precision medicine. Another major application disease modeling, especially hereditary diseases difficult to model vitro modeled by combining genome editing technologies. Herein, we introduce development current advances technology field. We focus on applications basic biology clinical research, also highlight limitations future perspectives. hope this review provide a valuable reference developments organoids.

Language: Английский

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Human organoids: New strategies and methods for analyzing human development and disease

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2756 - 2769

Published: July 1, 2022

For decades, insight into fundamental principles of human biology and disease has been obtained primarily by experiments in animal models. While this allowed researchers to understand many biological processes great detail, some developmental mechanisms have proven difficult study due inherent species differences. The advent organoid technology more than 10 years ago established laboratory-grown organ tissues as an additional model system recapitulate human-specific aspects biology. use 3D organoids, well other advances single-cell technologies, revealed unprecedented insights mechanisms, especially those that distinguish humans from species. This review highlights novel with a focus on how generated better understanding development disease.

Language: Английский

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Microfluidic organoids-on-a-chip: The future of human models

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 144, P. 41 - 54

Published: Oct. 11, 2022

Language: Английский

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Progress in multicellular human cardiac organoids for clinical applications

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(4), P. 503 - 514

Published: April 1, 2022

Language: Английский

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Multi-chamber cardioids unravel human heart development and cardiac defects

Cell, Journal Year: 2023, Volume and Issue: 186(25), P. 5587 - 5605.e27

Published: Nov. 28, 2023

The number one cause of human fetal death are defects in heart development. Because the embryonic is inaccessible and impacts mutations, drugs, environmental factors on specialized functions different compartments not captured by vitro models, determining underlying causes difficult. Here, we established a cardioid platform that recapitulates development all major compartments, including right left ventricles, atria, outflow tract, atrioventricular canal. By leveraging 2D 3D differentiation, efficiently generated progenitor subsets with distinct first, anterior, posterior second field identities. This advance enabled reproducible generation cardioids compartment-specific vivo-like gene expression profiles, morphologies, functions. We used this to unravel ontogeny signal contraction propagation between interacting chambers dissect how teratogens, drugs developing heart.

Language: Английский

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Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 26, 2024

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable genetic engineering, can be differentiated into most somatic types. been widely applied model human development diseases, perform drug screening, develop therapies. In this review, we outline key developments iPSC field highlight immense versatility of modeling therapeutic applications. We begin by discussing pivotal discoveries that revealed potential a nucleus reprogramming led successful generation iPSCs. consider molecular mechanisms dynamics as well numerous methods available induce pluripotency. Subsequently, discuss various iPSC-based cellular models, from mono-cultures single type complex three-dimensional organoids, how these models elucidate diseases. use examples neurological disorders, coronavirus disease 2019 (COVID-19), cancer diversity disease-specific phenotypes modeled using iPSC-derived cells. also used high-throughput screening toxicity studies. Finally, process developing autologous allogeneic therapies their alleviate

Language: Английский

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