0e9ec2b8-4a9f-4705-9c08-2a7bdd9dd353 - samples
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PROVIDER: EGAD00001011289 | EGA |
REPOSITORIES: EGA
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Project description:The generation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offers an unlimited source of patient-specific human cardiomyocytes. However, the use of iPSC-CM in vitro-models to guide the clinic selection of particular drugs for individual patients remains a vision. A major limitation represents the immature phenotype of iPSC-CMs, which alters their sensitivity towards physiological and pathophysiological stimuli, cardioactive drugs or toxic substances, in comparison to adult cardiomyocytes (CMs). In this study, we aim to generate iPSC-CMs with an advanced maturation state by combining the use of MM with the alignment of the cells on nanopatterned surfaces (NP) and induction of an increased contractile workload by electrical stimulation (ES). Under the combined influence of MM, NP and ES, iPSC-CMs develop a more complex cellular structure, increased mitochondrial content and enhanced electrophysiological properties. Furthermore, the response of iPSC-CMs matured under influence of MM, NP and ES to isoprenaline as well as verapamil differs to less mature iPSC-CMs cultured in B27-medium. Taken together, our results reveal that the combination of MM, NP and ES strongly improves the maturation state of iPSC-CMs and that this advanced maturation state critically affects the cell behavior in functional studies as well as response to cardioactive drugs.
| EGAS00001007491 | EGA
Project description:To improve the maturity of iPSC-cardiomyocytes, we addressed the cell type specification of iPSC-cardiomyocytes by microarray and analyzed in detail about cardiac maturation process. We compared gene expression between samples, and extracted several key genes for cardac maturation and check the function of these genes. We show that a number of genes expression correlate with cardiac maturation process, and found surface markers to discriminate differentiated cardiomyocytes from other immature cells.
2018-08-31 | GSE72611 | GEO
Project description:Rationale: Monitoring and controlling cardiomyocyte activity with optogenetic tools offers exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level. Objective: To test the hypothesis that cardiomyocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electrical activity in isolated cardiomyocytes and the whole heart as well as function and maturity in induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Methods and Results: We first generated mice with cardiomyocyte-restricted expression of VSFP2.3 and demonstrated distinct sarcolemmal localization of VSFP2.3 without any signs for associated pathologies (assessed by echocardiography). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch-clamping. The utility of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiomyocytes. Optical cardiograms (OCGs) could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in iPSC-derived cardiomyocytes. Conclusions: We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof-of-concept for its utility in optogenetic sensing of physiological and pathological excitation in mature and immature cardiomyocytes in vitro and in vivo. Determination of transgene (VSFP2.3) cardiotoxicity
2015-09-02 | E-GEOD-69190 | biostudies-arrayexpress
Project description:To improve the maturity and reduce the heterogeneity of iPSC-cardiomyocytes, we addressed the diversity of iPSC-cardiomyocytes by single-cell RNA sequencing and analyzed in detail about heterogeneity during cardiac maturation process.
2018-08-31 | GSE72612 | GEO
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
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 | GSE239317 | GEO
Project description:iPSC-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. In this study, we describe a maturation media (MM) designed to provide oxidative substrates adapted to the metabolic needs of hiPSC-CMs as compared to standard RPMI/B27 media. RNA sequencing was performed to gain insight into the underlying molecular basis for the changes. Compared to baseline (day 21) conditions, three weeks subsequent exposure to MM (day 41) caused a significant differential expression in genes. GO analysis of the MM-differentially upregulated genes were informative, mapping to mitochondrial metabolism. Additionally, multiple Ca2+ cycling/sarcoplasmic reticulum (SR), sarcomeric, and ion channel genes were differentially expressed. These gene expression changes indicated that supplementation with oxidative substrates and subsequent metabolic changes might affect cardiomyocyte electrophysiology, Ca2+ cycling and contractility.
2020-06-30 | GSE151279 | GEO
Project description:We treated differentiated iPSC-derived cardiomyocytes with a small molecule FOXO activator to to evaluate potential genes that might facilitate cardiomyocyte maturation.
2024-08-09 | GSE190742 | GEO
Project description:Using APEX2, an engineered peroxidase, as an imaging tag, we successfully located iPSC-derived cardiomyocytes (iPSC-CMs) engrafted in post-myocardial infarction mouse hearts for more than 6 months. APEX2 caused clear contrast in X-ray microscopy and electron microscopy, and relatively well organized sarcomere structures were formed in iPSC-CMs. Electron microscopic tomography further found the development of T-tubules and dyads in APEX2-labelled cells, which are the signature characteristics of the maturation of cardiomyocytes.
2018-12-01 | GSE99470 | GEO
Project description:Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes, iCMs) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CM and iCM are still unknown. Here we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status while iCMs exhibit maturation status that more resemble adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis while iCMs utilize fatty acid oxidation as the main pathway. Importantly, iPSC-CMs and iCMs exhibit different cell cycle status, alteration of which influenced their maturation. Therefore, our study provides a foundation for understanding the pros and cons of different reprogramming approaches.
2017-09-26 | GSE99814 | GEO