Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes

Tohyama, Shugo; Fujita, Jun; Fujita, Chihana; Yamaguchi, Miho; Kanaami, Sayaka; Ohno, Rei; Sakamoto, Kazuho; Kodama, Motomune; Kurokawa, Junko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Okada, Marina; Nakajima, Kiyokazu; Tanosaki, Sho; Someya, Shota; Hirano, Akinori; Kawaguchi, Shinji; Kobayashi, Eiji; Fukuda, Keiichi

doi:10.1016/j.stemcr.2017.08.025

Cited by 96 publications

(82 citation statements)

References 31 publications

(48 reference statements)

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“…Additionally, risk of tumorigenesis remains an underlying concern of pluripotent stem cell-based therapies and has been detected in immunodeficient mouse models 75,76 . However, improvements have been made in generating mature iPSC-derived cardiomyocytes with high purity and sufficient numbers, and these improvements are expected to enhance the cell retention rate by increasing the number of transplanted cells and to reduce the risk of tumorigenesis and arrhythmia associated with undifferentiated immature cells 77,78 . In addition, providing scaffolds for iPSC-derived cardiomyocytes, such as hydrogels or cell sheets, has been shown to improve therapeutic outcomes 79,80 .…”

Section: Cell-based Therapies For Cardiac Repairmentioning

confidence: 99%

Therapeutic approaches for cardiac regeneration and repair

2018

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Ischaemic heart disease is a leading cause of death worldwide. Injury to the heart is followed by loss of the damaged cardiomyocytes, which are replaced with fibrotic scar tissue. Depletion of cardiomyocytes results in decreased cardiac contraction, which leads to pathological cardiac dilatation, additional cardiomyocyte loss, and mechanical dysfunction, culminating in heart failure. This sequential reaction is defined as cardiac remodelling. Many therapies have focused on preventing the progressive process of cardiac remodelling to heart failure. However, after patients have developed end-stage heart failure, intervention is limited to heart transplantation. One of the main reasons for the dramatic injurious effect of cardiomyocyte loss is that the adult human heart has minimal regenerative capacity. In the past 2 decades, several strategies to repair the injured heart and improve heart function have been pursued, including cellular and noncellular therapies. In this Review, we discuss current therapeutic approaches for cardiac repair and regeneration, describing outcomes, limitations, and future prospects of preclinical and clinical trials of heart regeneration. Substantial progress has been made towards understanding the cellular and molecular mechanisms regulating heart regeneration, offering the potential to control cardiac remodelling and redirect the adult heart to a regenerative state.

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Section: Cell-based Therapies For Cardiac Repairmentioning

confidence: 99%

Therapeutic approaches for cardiac regeneration and repair

2018

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“…Recent advancements in differentiation techniques allowed the generation of functional CMs from hPSCs, demonstrated by their ability to express CM-specific markers that are considered as reliable and renewable cellular source for cardiac regeneration [1,8,9]. Various signaling pathways interact in a complex and sequential manner to drive cardiomyogenesis during development [10].…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells

Nemade

Acharya

Chaudhari

et al. 2020

Cells

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Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, the Wingless (Wnt) signaling pathway has emerged as the key regulator of cardiomyogenesis. In this study, we evaluated the effects of cyclooxygenase inhibitors on cardiac differentiation of hPSCs. Cardiac differentiation was performed by adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency of cardiac differentiation was evaluated by flow cytometry and RT-qPCR. Generated hPSC-CMs were characterised using immunocytochemistry, electrophysiology, electron microscopy, and calcium transient measurements. Our data show that the COX inhibitors Sulindac and Diclofenac in combination with CHIR99021 (GSK-3 inhibitor) efficiently induce cardiac differentiation of hPSCs. In addition, inhibition of COX using siRNAs targeted towards COX-1 and/or COX-2 showed that inhibition of COX-2 alone or COX-1 and COX-2 in combination induce cardiomyogenesis in hPSCs within 12 days. Using IMR90-Wnt reporter line, we showed that inhibition of COX-2 led to downregulation of Wnt signalling activity in hPSCs. In conclusion, this study demonstrates that COX inhibition efficiently induced cardiogenesis via modulation of COX and Wnt pathway and the generated cardiomyocytes express cardiac-specific structural markers as well as exhibit typical calcium transients and action potentials. These cardiomyocytes also responded to cardiotoxicants and can be relevant as an in vitro cardiotoxicity screening model.

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“…tried to use glucose‐depleted medium containing abundant lactate to remove non‐CM cells via the metabolic difference of CMs versus non‐CM cells. They showed an increase in the purity of the PSC‐derived CMs, but did not demonstrate any enhanced maturation of the cells …”

Section: Remaining Challenges Of Using Pscs For MI Therapymentioning

confidence: 93%

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Jiang

Shamul

et al. 2020

Advanced Therapeutics

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Myocardial infarction (MI) is a life‐threatening disease resulting from the irreversible death of cardiomyocytes (CMs). Stem cell‐based therapies have been studied for MI treatment over the last two decades with promising outcomes. Here, the past work in this field is critically reviewed to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. Overall, PSCs (particularly iPSCs) have more advantages than the other cells for cardiac regeneration. However, the use of iPSCs is also facing critical challenges, which may be resolved by using biomaterials to engineer stem cells for reduced immunogenicity, improved immobilization/survival in the heart, and increased integration with the host cardiac tissue to eliminate arrhythmia. Biomaterials have also been applied in the derivation of CMs in vitro to increase the efficiency and maturation of cardiac differentiation. Collectively, a lot has been learned from the past failures of simply injecting intact stem cells or their derivatives in vivo for treating MI, and bioengineering stem cells with biomaterials may be a valuable strategy for advancing stem cell therapy towards its widespread application for MI treatment in the clinic.

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Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes

Cited by 96 publications

References 31 publications

Therapeutic approaches for cardiac regeneration and repair

Therapeutic approaches for cardiac regeneration and repair

Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

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