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Modeling Radiation-induced Cardiovascular Dysfunction with Human iPSC-Derived Engineered Heart Tissues

ABSTRACT: Modeling Radiation-induced Cardiovascular Dysfunction with Human iPSC-Derived Engineered Heart Tissues

PROVIDER: PRJNA1011335 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25844563_1.fastq.gz	Fastqsanger.gz
	SRR25844563_2.fastq.gz	Fastqsanger.gz
	SRR25844564_1.fastq.gz	Fastqsanger.gz
	SRR25844564_2.fastq.gz	Fastqsanger.gz
	SRR25844565_1.fastq.gz	Fastqsanger.gz

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Modeling Radiation-induced Cardiovascular Dysfunction with Human iPSC-Derived Engineered Heart Tissues

Project description:Low-LET radiation can cause cardiovascular dysfunctions at high-dose rates. For example, photons used in thoracic radiotherapy are known to cause acute cardiac tissue damage with elevated serum cardiac Troponin I level and long-term cardiac complications when delivered as fractionated exposures at high-dose rates. However, the effects of continuous low-dose rate radiation exposure on the heart, which simulate the space radiation environment, have not been well-studied. In this study, we aim to model low-LET space radiation-induced cardiovascular dysfunction using human induced pluripotent stem cell (iPSC)-derived engineered heart tissues (EHTs) exposed to protracted γ-ray irradiation. The investigation of pathophysiological changes in this model may provide insights and guide the development of countermeasures. As a proof-of-principle for the application of this model in drug development, we also tested the protective effect of a mitochondrial-specific antioxidant, MitoTempo, on irradiated EHTs.

2023-09-05 | GSE242108 | GEO

Modeling ionizing radiation-induced cardiovascular dysfunction with human iPSC-derived engineered heart tissues.

Project description: Not available

| S-EPMC10961094 | biostudies-literature

Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging

Project description:Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) sets their identity back to an embryonic age. This presents a fundamental hurdle for modeling late-onset disorders using iPSC-derived cells. We therefore developed a strategy to induce age-like features in multiple iPSC-derived lineages and tested its impact on modeling Parkinson’s disease (PD). We first describe markers that predict fibroblast donor age and observed the loss of these age-related markers following iPSC induction and re-differentiation into fibroblasts. Remarkably, age-related markers were readily induced in iPSC-derived fibroblasts or neurons following exposure to progerin including dopamine neuron-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes requiring both aging and genetic susceptibility such as frank dendrite degeneration, progressive loss of tyrosine-hydroxylase expression and enlarged mitochondria or Lewy body-precursor inclusions. Our study presents a strategy for inducing age-related cellular properties and enables the modeling of late-onset disease features. Induced pluripotent stem cell-derived midbrain dopamine neurons from a young and old donor overexpressing either GFP or Progerin.

2014-01-23 | E-GEOD-52431 | biostudies-arrayexpress

Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation

Project description:Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation

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Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation [I]

Project description:Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation [I]

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Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation [II]

Project description:Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation [II]

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Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation [II]

Project description:Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treatable with antiarrhythmic drugs, but patient responses are highly variable. Human induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) are useful for discovering precision therapeutics, but current platforms yield an immature cellular phenotype and are not easily scalable for high-throughput screening. Here, we report that primary adult atrial, but not ventricular, fibroblasts induced greater functional iPSC-aCM maturation, partly through connexin-40 and ephrin-B1 signaling. We developed a protein patterning process within industry-standard multiwell plates to engineer patterned co-culture (PC) of iPSC-aCMs and atrial fibroblasts that significantly enhanced iPSC-aCM structural, electrical, contractile, and metabolic maturation for 6+ weeks versus conventional mono-/co-cultures. PC displayed greater sensitivity for detecting drug efficacy than monocultures, and enabled the modeling and pharmacological or gene editing treatment of an AF-like electrophysiological phenotype due to a sodium channel mutation. In conclusion, PC is useful to elucidate heterotypic cell signaling in the atria, drug screening, and to model AF.

2024-01-19 | GSE239321 | GEO

Engineered co-cultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation [I]

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Human iPSC-based Modeling of Late-Onset Disease using Progerin-induced Aging

2014-01-23 | GSE52431 | GEO

Modeling Atrial Fibrillation (AF) in a Dish using Atrial iPSC-Derived Cardiomyocytes (iPSC-CMs)

Project description:Our study aims to illustrate the potential use of atrial iPSC-CMs for modeling AF in a dish, elucidating the underlying cellular mechanisms, and identifying novel mechanism-based therapies custom-tailored for individual patients

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