Practical adoption of state-of-the-art hiPSC-cardiomyocyte differentiation techniques

Rupert, Cassady E.; Irofuala, Chinedu; Coulombe, Kareen L K

doi:10.1371/journal.pone.0230001

Cited by 19 publications

(20 citation statements)

References 34 publications

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“…Further, relaxation time T50 increases in the high VEGF loaded group at 4 weeks, suggesting increased contractile work with high VEGF at late time points with little effect on excitability as measured by maximum capture rate (Supplemental Figure S4). The mechanical characteristics of these engineered hiPSC-derived cardiomyocyte tissues are within the same magnitude that we have reported by our group previously [50][51][52] and other engineered hiPSC-CM tissues [53][54][55][56][57].These data suggest that transient VEGF release had little influence on the mechanical function of hiPSC-derived cardiomyocytes in engineered tissues.…”

Section: Engineered Cardiac Tissue Function Is Preserved With Vegf-releasing Microspheressupporting

confidence: 86%

Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts

et al. 2020

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Heart regeneration after myocardial infarction requires new cardiomyocytes and a supportive vascular network. Here, we evaluate the efficacy of localized delivery of angiogenic factors from biomaterials within the implanted muscle tissue to guide growth of a more dense, organized, and perfused vascular supply into implanted engineered human cardiac tissue on an ischemia/ reperfusion injured rat heart. We use large, aligned 3-dimensional engineered tissue with cardiomyocytes derived from human induced pluripotent stem cells in a collagen matrix that contains dispersed alginate microspheres as local protein depots. Release of angiogenic growth factors VEGF and bFGF in combination with morphogen sonic hedgehog from the microspheres into the local microenvironment occurs from the epicardial implant site. Analysis of the 3D vascular network in the engineered tissue via Microfil® perfusion and microCT imaging at 30 days shows increased volumetric network density with a wider distribution of vessel diameters, proportionally increased branching and length, and reduced tortuosity. Global heart function is increased in the angiogenic factor-loaded cardiac implants versus sham. These findings demonstrate for the first time the efficacy of a combined remuscularization and revascularization therapy for heart regeneration after myocardial infarction.

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Section: Engineered Cardiac Tissue Function Is Preserved With Vegf-releasing Microspheressupporting

confidence: 86%

Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts

et al. 2020

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“…Many cardiac purification protocols involve the use of vectors that incorporate their genetic material to the host cells, thus rendering this strategy non suitable for clinical applications [98][99][100][101]. Nevertheless, strategies exist to purify myocytes without altering their genome, with lactate selection gaining popularity [37,40,42,46,97,195,[212][213][214][215]. However, they are immature CMs.…”

Section: Discussionmentioning

confidence: 99%

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Bizy

Klos

2020

Animals

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Heart failure (HF) is a common disease in which the heart cannot meet the metabolic demands of the body. It mostly occurs in individuals 65 years or older. Cardiac transplantation is the best option for patients with advanced HF. High numbers of patient-specific cardiac myocytes (CMs) can be generated from induced pluripotent stem cells (iPSCs) and can possibly be used to treat HF. While some studies found iPSC-CMS can couple efficiently to the damaged heart and restore cardiac contractility, almost all found iPSC-CM transplantation is arrhythmogenic, thus hampering the use of iPSC-CMs for cardiac regeneration. Studies show that iPSC-CM cultures are highly heterogeneous containing atrial-, ventricular- and nodal-like CMs. Furthermore, they have an immature phenotype, resembling more fetal than adult CMs. There is an urgent need to overcome these issues. To this end, a novel and interesting avenue to increase CM maturation consists of modulating their metabolism. Combined with careful engineering and animal models of HF, iPSC-CMs can be assessed for their potential for cardiac regeneration and a cure for HF.

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“…Cardiac purity was measured by ow cytometry analysis as previously described. 85 Human Cardiac Fibroblast Culture.…”

Section: Methodsmentioning

confidence: 99%

A Predictive in Vitro Risk Assessment Platform for Pro-Arrhythmic Toxicity Using Human 3D Cardiac Microtissues

Kofron

Kim

Munarin

et al. 2021

Preprint

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Cardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.

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Practical adoption of state-of-the-art hiPSC-cardiomyocyte differentiation techniques

Cited by 19 publications

References 34 publications

Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts

Engineered human myocardium with local release of angiogenic proteins improves vascularization and cardiac function in injured rat hearts

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

A Predictive in Vitro Risk Assessment Platform for Pro-Arrhythmic Toxicity Using Human 3D Cardiac Microtissues

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