Author Correction: Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Ronaldson-Bouchard, Kacey; Stephen, P.; Yeager, Keith; Chen, Timothy; Song, LouJin; Sirabella, Dario; Morikawa, Kumi; Teles, Diogo; Yazawa, Masayuki; Vunjak‐Novakovic, Gordana

doi:10.1038/s41586-019-1415-9

Cited by 19 publications

(19 citation statements)

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“…Interestingly, this intensity training was most successful for engineered heart tissues derived from 'early-stage' hPSC-CMs (that is, generated soon after the first spontaneous contractions are observed) but not for those derived from hPSC-CMs that had been in culture for longer time periods (~4 weeks) 148 . As a cautionary note, the authors published an erratum in 2019 detailing numerous errors in the original manuscript, including the use of an in vivo electron micrograph that was described as EHT 172 .…”

Section: Moving To 3d Cultures: Engineered Heart Tissues Mechanical mentioning

confidence: 99%

Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine

et al. 2020

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Our knowledge of pluripotent stem cell (PSC) biology has advanced to the point where we now can generate most cells of the human body in the laboratory. PSC-derived cardiomyocytes can be generated routinely with high yield and purity for disease research and drug development, and these cells are now gradually entering the clinical research phase for the testing of heart regeneration therapies. However, a major hurdle for their applications is the immature state of these cardiomyocytes. In this Review, we describe the structural and functional properties of cardiomyocytes and present the current approaches to mature PSC-derived cardiomyocytes. To date, the greatest success in maturation of PSC-derived cardiomyocytes has been with transplantation into the heart in animal models and the engineering of 3D heart tissues with electromechanical conditioning. In conventional 2D cell culture, biophysical stimuli such as mechanical loading, electrical stimulation and nanotopology cues all induce substantial maturation, particularly of the contractile cytoskeleton. Metabolism has emerged as a potent means to control maturation with unexpected effects on electrical and mechanical function. Different interventions induce distinct facets of maturation, suggesting that activating multiple signalling networks might lead to increased maturation. Despite considerable progress, we are still far from being able to generate PSC-derived cardiomyocytes with adult-like phenotypes in vitro. Future progress will come from identifying the developmental drivers of maturation and leveraging them to create more mature cardiomyocytes for research and regenerative medicine.

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Section: Moving To 3d Cultures: Engineered Heart Tissues Mechanical mentioning

confidence: 99%

Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine

et al. 2020

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“…Specifically, these authors found that the ratio of 70% hPSC-derived CMs and 30% human foreskin FBs was optimal for promoting maturation at the cellular and tissue levels [51]. Many subsequent studies have confirmed the significance of including non-myocytes in engineered cardiac constructs [32,36,51,53,55,[101][102][103][104].…”

Section: Non-myocytesmentioning

confidence: 96%

“…The formation of these bundles results in self-alignment and anisotropic organization of CMs, which is a hallmark of cell maturation. Moreover, these constructs provide an easy way to analyze the electrical and mechanical properties of CMs, thus enabling the readily evaluation of their maturation state and facilitating their use in drug screening and toxicity assessment platforms [16,36,40,48,50,51,55,[145][146][147].…”

Section: Hydrogelsmentioning

confidence: 99%

Engineering and Assessing Cardiac Tissue Complexity

Tadevosyan

Iglesias-García

Mazo

et al. 2021

IJMS

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Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. However, reproducing tissue-like properties is still a pending issue, as constructs generated to date remain immature relative to native adult heart. Moreover, there is a high degree of heterogeneity in the methodologies used to assess the functionality and cardiac maturation state of engineered cardiac tissue constructs, which further complicates the comparison of constructs generated in different ways. Here, we present an overview of the general approaches developed to generate functional cardiac tissues, discussing the different cell sources, biomaterials, and types of engineering strategies utilized to date. Moreover, we discuss the main functional assays used to evaluate the cardiac maturation state of the constructs, both at the cellular and the tissue levels. We trust that researchers interested in developing engineered cardiac tissue constructs will find the information reviewed here useful. Furthermore, we believe that providing a unified framework for comparison will further the development of human engineered cardiac tissue constructs displaying the specific properties best suited for each particular application.

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“…7 Of note, an erratum was published in 2019 where authors described a number of errors in the original manuscript. 10 Subsequent reports have determined that it may take at least 6 weeks for tissues to display significant maturation using electrical stimulation, 11,12 making it low throughput for in vitro applications and not amenable for generation of a large enough number of CMs for in vivo applications. In one report, tissues required 6 weeks of electrical stimulation in order to display a significant force increase in response to the inotropic HF drug milrinone.…”

Section: Significance Statementmentioning

confidence: 99%

“…Interestingly, robust maturation was observed only in tissues seeded with early‐stage (D12) but not with later‐stage hiPSC‐CMs (D28), which suggests higher plasticity of the early differentiated cells 7 . Of note, an erratum was published in 2019 where authors described a number of errors in the original manuscript 10 . Subsequent reports have determined that it may take at least 6 weeks for tissues to display significant maturation using electrical stimulation, 11,12 making it low throughput for in vitro applications and not amenable for generation of a large enough number of CMs for in vivo applications.…”

Section: Cardiac Microtissue Maturationmentioning

confidence: 99%

Engineered Human Cardiac Microtissues: The State-of-the-(He)art

2021

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Due to the integration of recent advances in stem cell biology, materials science, and engineering, the field of cardiac tissue engineering has been rapidly progressing toward developing more accurate functional 3D cardiac microtissues from human cell sources. These engineered tissues enable screening of cardiotoxic drugs, disease modeling (eg, by using cells from specific genetic backgrounds or modifying environmental conditions) and can serve as novel drug development platforms. This concise review presents the most recent advances and improvements in cardiac tissue formation, including cardiomyocyte maturation and disease modeling.

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Author Correction: Advanced maturation of human cardiac tissue grown from pluripotent stem cells

Cited by 19 publications

References 1 publication

Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine

Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine

Engineering and Assessing Cardiac Tissue Complexity

Engineered Human Cardiac Microtissues: The State-of-the-(He)art

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