Feeder-free generation and characterization of endocardial and cardiac valve cells from human pluripotent stem cells

Liu, Clifford Z.; Prasad, Aditi; Jadhav, Bharati; Liu, Yu; Gu, Mingxia; Sharp, Andrew J.; Gelb, Bruce D.

doi:10.1016/j.isci.2023.108599

Cited by 3 publications

(2 citation statements)

References 74 publications

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“…One of the major avenues is for cardiac cells to be derived by differentiating human-induced pluripotent stem cells (iPSCs) or embryonic stem cells to cardiac lineages using signaling or environmental cues. Examples range from 2-dimensional cultures of cardiomyocytes, 98 epicardial cells, 99 and endocardial cells 100 to selforganizing organoid models with complex 3-dimensional structures. 101 Clinical implementation of stem cell-based technologies applied to the heart includes the recent development of 3-dimensional cardiac microtissues engineered from iPSCs harboring human mutations, allowing for rapid testing of potential therapeutics for correction of genetic defects and promotion of cardiac regeneration.…”

Section: Cardiac Cells In a Dish: In Vitro Systemsmentioning

confidence: 99%

Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

Palmer,

Rosenthal,

Teichmann

et al. 2024

Circulation Research

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Throughout our lifetime, each beat of the heart requires the coordinated action of multiple cardiac cell types. Understanding cardiac cell biology, its intricate microenvironments, and the mechanisms that govern their function in health and disease are crucial to designing novel therapeutical and behavioral interventions. Recent advances in single-cell and spatial omics technologies have significantly propelled this understanding, offering novel insights into the cellular diversity and function and the complex interactions of cardiac tissue. This review provides a comprehensive overview of the cellular landscape of the heart, bridging the gap between suspension-based and emerging in situ approaches, focusing on the experimental and computational challenges, comparative analyses of mouse and human cardiac systems, and the rising contextualization of cardiac cells within their niches. As we explore the heart at this unprecedented resolution, integrating insights from both mouse and human studies will pave the way for novel diagnostic tools and therapeutic interventions, ultimately improving outcomes for patients with cardiovascular diseases.

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Section: Cardiac Cells In a Dish: In Vitro Systemsmentioning

confidence: 99%

Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

Palmer,

Rosenthal,

Teichmann

et al. 2024

Circulation Research

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“…Over the past decade, advances in iPSC differentiation have enabled researchers to generate robust populations of many different cell types. Recent studies have produced reliable protocols for stem cell differentiation to a variety of heart cell types, including ventricular cardiomyocytes [12], [13][14][15][16][17][18], atrial cardiomyocytes [16,19], epicardial cells [9,[20][21][22], cardiac endothelial cells [23,24], cardiac fibroblasts [25][26][27], and nodal cells. [28][29][30] These iPSC-derived cells can be used to model human heart cell behavior and wound repair processes.…”

Section: Introductionmentioning

confidence: 99%

Engineered Cardiac Microtissue Biomanufacturing Using Human Induced Pluripotent Stem Cell Derived Epicardial Cells

Butler,

Ahmed,

Jablonski

et al. 2024

Preprint

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Epicardial cells are a crucial component in constructing in vitro 3D tissue models of the human heart, contributing to the ECM environment and the resident mesenchymal cell population. Studying the human epicardium and its development from the proepicardial organ is difficult, but induced pluripotent stem cells can provide a source of human epicardial cells for developmental modeling and for biomanufacturing heterotypic cardiac tissues. This study shows that a robust population of epicardial cells (approx. 87.7% WT1+) can be obtained by small molecule modulation of the Wnt signaling pathway. The population maintains WT1 expression and characteristic epithelial morphology over successive passaging, but increases in size and decreases in cell number, suggesting a limit to their expandability in vitro. Further, low passage number epicardial cells formed into more robust 3D microtissues compared to their higher passage counterparts, suggesting that the ideal time frame for use of these epicardial cells for tissue engineering and modeling purposes is early on in their differentiated state. Additionally, the differentiated epicardial cells displayed two distinct morphologic sub populations with a subset of larger, more migratory cells which led expansion of the epicardial cells across various extracellular matrix environments. When incorporated into a mixed 3D co-culture with cardiomyocytes, epicardial cells promoted greater remodeling and migration without impairing cardiomyocyte function. This study provides an important characterization of stem cell-derived epicardial cells, identifying key characteristics that influence their ability to fabricate consistent engineered cardiac tissues.

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Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping

Henderson,

Alqahtani,

Chaudhry

et al. 2024

Disease Models &Amp; Mechanisms

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Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate. However, several other factors are likely to contribute. For example, the level of patient phenotyping required for clinical care may be insufficient for research studies focused on mechanistic discovery. Although several hundred mouse gene knockouts have been described with CHDs, these are generally not phenotyped and described in the same way as CHDs in patients, and thus are not readily comparable. Moreover, most patients with CHDs carry variants of uncertain significance of crucial cardiac genes, further complicating comparisons between humans and mouse mutants. In spite of major advances in cardiac developmental biology over the past 25 years, these advances have not been well communicated to geneticists and cardiologists. As a consequence, the latest data from developmental biology are not always used in the design and interpretation of studies aimed at discovering the genetic causes of CHDs. In this Special Article, while considering other in vitro and in vivo models, we create a coherent framework for accurately modelling and phenotyping human CHDs in mice, thereby enhancing the translation of genetic and genomic studies into the causes of CHDs in patients.

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Feeder-free generation and characterization of endocardial and cardiac valve cells from human pluripotent stem cells

Cited by 3 publications

References 74 publications

Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

Revisiting Cardiac Biology in the Era of Single Cell and Spatial Omics

Engineered Cardiac Microtissue Biomanufacturing Using Human Induced Pluripotent Stem Cell Derived Epicardial Cells

Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping

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