Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown
Published: March 27, 2025
Language: Английский
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
Citations
78
Cell stem cell, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 1, 2024
Language: Английский
Citations
8
Stem Cells Translational Medicine, Journal Year: 2024, Volume and Issue: 13(5), P. 425 - 435
Published: March 19, 2024
Abstract The ultimate goal of cardiac tissue engineering is to generate new muscle repair or replace the damaged heart. This requires advances in stem cell technologies differentiate billions cardiomyocytes, together with advanced biofabrication approaches such as 3D bioprinting achieve requisite structure and contractile function. In this concise review, we cover recent progress using pluripotent cell-derived key design criteria for aligned tissues, ongoing challenges field that must be addressed realize goal.
Language: Английский
Citations
7
European Heart Journal, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 13, 2024
Abstract Cardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and models. In response, the recently enacted Food Drug Administration Modernization Act 2.0 encourages alternative approaches including induced pluripotent stem cells (iPSCs). Human iPSCs provide patient-specific, precise, screenable platform testing, paving way cardiovascular precision medicine. This review discusses milestones in iPSC differentiation their applications disease modelling discovery It then explores challenges emerging opportunities implementation of ‘clinical trials in-a-dish’. Concluding, this proposes framework future clinical trial design with strategic incorporations technology, microphysiological systems, pan-omics, artificial intelligence improve success advance healthcare.
Language: Английский
Citations
7
Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 250 - 250
Published: Jan. 29, 2024
The human heart lacks significant regenerative capacity; thus, the solution to failure (HF) remains organ donation, requiring surgery and immunosuppression. demand for constructed cardiac tissues (CCTs) model treat disease continues grow. Recent advances in induced pluripotent stem cell (iPSC) manipulation, CRISPR gene editing, 3D tissue culture have enabled a boom iPSC-derived CCTs (iPSC-CCTs) with diverse types architecture. Compared 2D-cultured cells, iPSC-CCTs better recapitulate biology, demonstrating potential advance modeling, drug discovery, medicine, though could benefit from methods faithfully mimic physiology electrophysiology. Here, we summarize future developments vascularization, immunization, maturation of study therapy.
Language: Английский
Citations
6
Bioactive Materials, Journal Year: 2024, Volume and Issue: 40, P. 88 - 103
Published: June 9, 2024
Language: Английский
Citations
6
Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)
Published: Feb. 5, 2024
Transcription factors HAND1 and HAND2 (HAND1/2) play significant roles in cardiac organogenesis. Abnormal expression deficiency of HAND1/2 result severe defects. However, the function mechanism regulating human early lineage commitment differentiation are still unclear. With NKX2.5eGFP H9 embryonic stem cells (hESCs), we established single double knockout cell lines for HAND2, respectively, whose cardiomyocyte efficiency could be monitored by assessing NKX2.5-eGFP+ with flow cytometry. The specific markers heart fields subtypes was examined quantitative PCR, western blot immunofluorescence staining. Microelectrode array whole-cell patch clamp were performed to determine electrophysiological characteristics differentiated cardiomyocytes. transcriptomic changes HAND revealed RNA sequencing. target genes identified validated experimentally integrating chromatin immunoprecipitation sequencing data. Either or did not affect kinetics, whereas depletion resulted delayed onset. biased mesoderm toward second field progenitors at expense first progenitors, leading increased atrial outflow tract markers, which further confirmed appearance atrial-like action potentials. By contrast, cardiomyocytes had reduced displayed ventricular-like HAND1/2-deficient hESCs more inclined its derived potentials than during differentiation. Further mechanistic investigations suggested TBX5 as one downstream targets HAND1/2, overexpression partially restored abnormal hESCs. have redundant These findings only reveal essential organogenesis, but also provide important information on pathogenesis deficiency-related congenital diseases, potentially lead new therapeutic strategies.
Language: Английский
Citations
5
Cell stem cell, Journal Year: 2024, Volume and Issue: 31(3), P. 398 - 409.e5
Published: Feb. 15, 2024
The creation of a functional 3D bioprinted human heart remains challenging, largely due to the lack some crucial cardiac cell types, including atrioventricular canal (AVC) cardiomyocytes, which are essential slow down electrical impulse between atrium and ventricle. By utilizing single-cell RNA sequencing analysis bioprinting technology, we discover that stage-specific activation canonical Wnt signaling creates AVC cardiomyocytes derived from pluripotent stem cells. These display morphological characteristics express molecular markers transcription factors TBX2 MSX2. When in prefabricated tissues, these successfully delay impulse, demonstrating their capability functioning as vitro. Thus, findings not only identify key regulator cardiomyocyte differentiation vitro, but, more importantly, provide critical cellular source for biofabrication heart.
Language: Английский
Citations
5
Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)
Published: Sept. 23, 2024
Abstract The circadian clock is an evolutionarily conserved time-keeper that regulates physiological processes across 24 h. In the cardiovascular system, several parameters, such as blood pressure, heart rate, and metabolism, exhibit time-of-day variations. These features are in part driven by clock. Chronic perturbation of diurnal rhythmicity due to shift work or irregular social schedules has been associated with increased risk hypertension, arrhythmias, myocardial infarction. This review discusses impact rhythms on human health effect disruption occurrence adverse cardiac events. Additionally, we discuss how main factors diseases, obesity, sleep disorders, aging, affect rhythms. Finally, elaborate chronotherapy well targeting highlight novel approaches translate our scientific understanding into clinical practice.
Language: Английский
Citations
5
Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(18)
Published: March 12, 2024
Advanced in vitro models that recapitulate the structural organization and function of human heart are highly needed for accurate disease modeling, more predictable drug screening, safety pharmacology. Conventional 3D Engineered Heart Tissues (EHTs) lack heterotypic cell complexity culture under flow, whereas microfluidic Heart-on-Chip (HoC) general configuration contractile readouts. In this study, an innovative user-friendly HoC model is developed to overcome these limitations, by culturing pluripotent stem (hPSC)-derived cardiomyocytes (CMs), endothelial (ECs)- smooth muscle cells (SMCs), together with cardiac fibroblasts (FBs), underflow, leading self-organized miniaturized micro-EHTs (µEHTs) a CM-EC interface reminiscent physiological capillary lining. µEHTs cultured flow display enhanced performance conduction velocity. addition, presence EC layer altered responses µEHT contraction. This observation suggests potential barrier-like ECs, which may affect availability drugs CMs. These increased complexity, will pave way screen therapeutic targets predict efficacy.
Language: Английский
Citations
4