Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 154088 - 154088
Published: Feb. 1, 2025
Language: Английский
Nature Reviews Cardiology, Journal Year: 2020, Volume and Issue: 17(6), P. 341 - 359
Published: Feb. 3, 2020
Language: Английский
Citations
583
Circulation Research, Journal Year: 2017, Volume and Issue: 120(9), P. 1487 - 1500
Published: April 27, 2017
Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues different kinds are now generated routinely in many laboratories. Advances stem cell biology and engineering allow for generation constructs that come close to recapitulating complex structure heart muscle might, therefore, be amenable industrial (eg, drug screening) clinical repair) applications. Whether more physiological provides relevant advantage over standard 2-dimensional culture has yet shown head-to-head-comparisons. The present article gives an overview on current strategies with focus hydrogel methods discusses perspectives challenges necessary steps toward real-life application disease modeling, development, repair.
Language: Английский
Citations
207
Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)
Published: Jan. 7, 2020
The functions of the heart are achieved through coordination different cardiac cell subtypes (e.g., ventricular, atrial, conduction-tissue cardiomyocytes). Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) offer unique opportunities for research. Traditional studies using these cells focused on single-cells and utilized mixed populations. Our goal was to develop clinically-relevant engineered tissues (EHTs) comprised chamber-specific hPSC-CMs. Here we show that such EHTs can be generated by directing hPSCs differentiate into ventricular or atrial cardiomyocytes, then embedding in a collagen-hydrogel create chamber-specific, ring-shaped, EHTs. display distinct versus phenotypes as revealed immunostaining, gene-expression, optical assessment action-potentials conduction velocity, pharmacology, mechanical force measurements. We also establish an EHT-based arrhythmia model confirm its usefulness applying relevant pharmacological interventions. Thus, our EHT models used disease modeling, pathophysiological drug testing.
Language: Английский
Citations
200
Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8
Published: March 19, 2020
Cardiovascular diseases are the leading cause of death worldwide. Therefore, discovery induced pluripotent stem cells (iPSCs) and subsequent generation human cell-derived cardiomyocytes (hiPSC-CMs) was a pivotal point in regenerative medicine cardiovascular research. They constituted an appealing tool for replacing dead dysfunctional cardiac tissue, screening drugs toxins, studying inherited diseases. The problem is that these remain largely immature, order to utilize them, they must reach functional degree maturity. To attempt mimic
Language: Английский
Citations
200
Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)
Published: May 20, 2019
Abstract Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native impedes investigations CF biology their role Human pluripotent stem cells (hPSCs) provide a highly renewable genetically defined cell source, but efficient methods to generate hPSCs have not been described. Here, we show differentiation using sequential modulation Wnt FGF signaling second field progenitors that efficiently give rise hPSC-CFs. hPSC-CFs resemble morphology, proliferation, gene expression, fibroblast marker production extracellular matrix myofibroblast transformation induced by TGFβ1 angiotensin II. Furthermore, exhibit more embryonic phenotype when compared fetal adult primary CFs. Co-culture with hPSC-derived cardiomyocytes distinctly alters the electrophysiological properties co-culture dermal fibroblasts. powerful source for research, drug discovery, precision medicine, therapeutic applications cardiac regeneration.
Language: Английский
Citations
159
Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(3), P. 413 - 423
Published: May 8, 2023
Abstract Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient’s immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing off-the-shelf products. Previously, we generated mouse human hypoimmune pluripotent (HIP) stem cells depleting HLA class I II molecules overexpressing CD47 ( B2M −/− CIITA + ). To determine whether this strategy is successful in non-human primates, engineered rhesus macaque HIP transplanted them intramuscularly into four macaques. The survived unrestricted 16 weeks immunocompetent recipients differentiated several lineages, whereas wild-type were vigorously rejected. We also endocrinologically active pancreatic islet showed they immunocompetent, diabetic humanized mice 4 ameliorated diabetes. HIP-edited primary islets 40 an recipient without immunosuppression, unedited quickly
Language: Английский
Citations
76
STAR Protocols, Journal Year: 2022, Volume and Issue: 3(3), P. 101560 - 101560
Published: Aug. 18, 2022
The methods for the culture and cardiomyocyte differentiation of human embryonic stem cells, later induced pluripotent cells (hiPSC), have moved from a complex uncontrolled systems to simplified relatively robust protocols, using knowledge cues gathered at each step. HiPSC-derived cardiomyocytes proven be useful tool in disease modelling, drug discovery, developmental biology, regenerative medicine. In this protocol review, we will highlight evolution protocols associated with hPSC culture, differentiation, sub-type specification, maturation. We also discuss somatic cell direct reprogramming cardiomyocyte-like cells.
Language: Английский
Citations
75
Circulation, Journal Year: 2022, Volume and Issue: 145(18), P. 1412 - 1426
Published: Jan. 28, 2022
Human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) have tremendous promise for application in cardiac regeneration, but their translational potential is limited by an immature phenotype. We hypothesized that large-scale manufacturing of mature hPSC-CMs could be achieved through culture on polydimethylsiloxane (PDMS)-lined roller bottles and the transplantation these cells would mediate better structural functional outcomes than with conventional hPSC-CM populations.We comprehensively phenotyped after vitro maturation 20 40 days either PDMS or standard tissue plastic substrates. All were generated from a transgenic hPSC line stably expressed voltage-sensitive fluorescent reporter to facilitate vivo electrophysiological studies, cardiomyocyte populations also analyzed immunocytochemistry, ultrastructure calcium imaging, bulk single-cell transcriptomics. next compared into guinea pig model myocardial infarction using end points including histology, optical mapping graft- host-derived action potentials, echocardiography, telemetric electrocardiographic monitoring.We demonstrated economic generation >1×108 per PDMS-lined bottle. Compared counterparts substrates, PDMS-matured exhibited increased gene expression more properties vitro. More important, intracardiac grafts formed myocytes showed greatly enhanced structure alignment, host-graft electromechanical integration, less proarrhythmic behavior, greater beneficial effects contractile function.We describe practical methods scaled provide first evidence yields vivo.
Language: Английский
Citations
74
Science Advances, Journal Year: 2024, Volume and Issue: 10(3)
Published: Jan. 19, 2024
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treatable with antiarrhythmic drugs; however, patient responses remain highly variable. Human induced pluripotent stem cell–derived atrial cardiomyocytes (iPSC-aCMs) are useful for discovering precision therapeutics, but current platforms yield phenotypically immature cells and not easily scalable high-throughput screening. Here, primary adult atrial, ventricular, fibroblasts greater functional iPSC-aCM maturation, partly through connexin-40 ephrin-B1 signaling. We developed a protein patterning process within multiwell plates to engineer patterned fibroblast coculture (PC) that significantly enhanced structural, electrical, contractile, metabolic maturation 6+ weeks compared conventional mono-/coculture. PC displayed sensitivity detecting drug efficacy than monoculture enabled modeling pharmacological or gene editing treatment of an AF-like electrophysiological phenotype due mutated sodium channel. Overall, elucidating cell signaling in atria, screening, AF.
Language: Английский
Citations
18
Scientific Reports, Journal Year: 2017, Volume and Issue: 7(1)
Published: July 10, 2017
Abstract Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as culture method with greater resemblance to human in comparison standard technique 2D monolayer (ML) format. I Na was measured ML or EHT using patch-clamp technique. density ~1.8 fold larger (−18.5 ± 1.9 pA/pF; n = 17) than (−10.3 1.2 23; p < 0.001), approaching densities reported CM. Inactivation kinetics, voltage dependency steady-state inactivation activation did not differ between were similar previously values Action potential recordings sharp microelectrodes showed velocities (219 15 V/s, 13) left ventricle (LV, 253 7 25). LV CM morphology subcellular V 1.5 distribution. hiPSC-CM biophysical properties The format promotes action towards adult values, indicating its usefulness model excitability cardiac tissue.
Language: Английский
Citations
168