Generation of Functional Murine Cardiac Myocytes From Induced Pluripotent Stem Cells

Mauritz, Christina; Schwanke, Kristin; Reppel, Michael; Neef, Stefan; Katsirntaki, Katherina; Maier, Lars S.; Nguemo, Filomain; Menke, Sandra; Haustein, Moritz; Hescheler, Juergen; Hasenfuß, Gerd; Martin, Ulrich

doi:10.1161/circulationaha.108.778795

Cited by 441 publications

(317 citation statements)

References 29 publications

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“…Considering the prominent role of Ca 2+ as a cellular second messenger in directing the fate of stem cells towards cardiac [19][20][21]. We postulated that one of the critical targets f o r i n d u c t i o n o f [ C a 2 + ] i s i g n a l i n g i n v o l v e d i n cardiomyogenesis could be the activation of purinergic receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular [Ca +2 ] i exerts multiple functions in the process of cardiac cell differentiation and early heart development depending upon the amplitude, space, and time of [Ca 2+ ] i signaling. Decoding the molecular mechanism of the multifaceted roles of [Ca 2+ ] i signaling will therefore not only contribute to decipher molecular pathways of cardiogenesis but also help to elaborate protocols for highly efficient cardiomyocyte differentiation from ES cells [18][19][20][21]. During embryonic heart formation, a couple of cardiogenic factors turn on Ca 2+ -dependent signaling pathways in cardiac progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

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Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

Mazrouei

Sharifpanah

Bekhite

et al. 2015

Purinergic Signalling

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Purinergic signaling may be involved in embryonic development of the heart. In the present study, the effects of purinergic receptor stimulation on cardiomyogenesis of mouse embryonic stem (ES) cells were investigated. ADP or ATP increased the number of cardiac clusters and cardiac cells, as well as beating frequency. Cardiac-specific genes showed enhanced expression of α-MHC, MLC2v, α-actinin, connexin 45 (Cx45), and HCN4, on both gene and protein levels upon ADP/ATP treatment, indicating increased cardiomyogenesis and pacemaker cell differentiation. Real-time RT-PCR analysis of purinergic receptor expression demonstrated presence of P2X1, P2X4, P2X6, P2X7, P2Y1, P2Y2, P2Y4, and P2Y6 on differentiating ES cells. ATP and ADP as well as the P2X agonists β,γ-methylenadenosine 5′-triphosphate (β,γ-MetATP) and 8-bromoadenosine 5′-triphosphate (8- Br

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

Mazrouei

Sharifpanah

Bekhite

et al. 2015

Purinergic Signalling

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show abstract

“…In 2008, three independent research groups reported the derivation of cardiomyocytes from murine iPSC using embryoid body-based and monolayer-based differentiation protocols [19][20][21]. Later, the capacity for derivation of cardiomyocyte-like cells was demonstrated with human iPSC generated using the 4-gene system (OCT4, SOX2, NANOG, and LIN28 transgenes) [15] and the three-gene system (OCT4, SOX2, and KLF4) plus a histone deacetylase inhibitor (valproic acid) [23].…”

Section: Brief Historical Overview Of the Attempts To Cultivate Rhythmentioning

confidence: 99%

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

Arabadjiev¹,

Petkova²,

Chakarov³

et al. 2014

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Citation: Arabadjiev A, Petkova R, Chakarov S, Pankov R, Zhelev N. We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells. AbstractHuman cell lines, including disease cell lines are often superior to routine animal models for the purposes of rapid and safe assessment of the effects of different agents that may modulate myocardial functioning under physiological and pathological conditions. There are several currently existing methodologies for derivation of cardiomyocyte-like cells by targeted differentiation from pluripotent cells and by reprogramming/ transdifferentiation from other types of cells (multipotent progenitors, somatic cells, etc). The present paper reviews the potential sources of cells capable of differentiation along the cardiomyocyte lineage; the existing methodologies for targeted differentiation, outlining the specificities of each method; and the markers for differentiation along the mesodermal and the cardiogenic lineage. The yield of robustly beating cells expressing cardio-specific proteins derived by any of the existing methods, however, still rarely exceeds 70-90 %, even with the newly developed approaches for increasing the differentiation capacity. There still is significant variance in the results obtained by different research groups and even between different experiments carried out in the same laboratory, with the same type of cells and same general type of protocol. Derivation of new lines of human pluripotent and multipotent stem cells according to standardised protocols and in completely defined; xeno-free conditions may increase the reliability and reproducibility of research and speed up the development of potential clinical applications.

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“…Because of their multilineage differentiation potential, pluripotent stem cells (PSCs), such as embryonic stem cells and iPS cells (vide infra), represent an ideal source from which to obtain CMCs: in fact, embryonic stem cells and iPS cells give rise to all the cell derivatives of the three germ layers (ectoderm, mesoderm and endoderm). [11][12][13] PSCs spontaneously differentiate into CMCs but, unfortunately, the efficiency of this process is extremely low (0.1-1%). Over the last few years, several methods have been proposed to improve the efficiency of this process; 14,15 however, inducing a cardiac fate is still extremely difficult, so easy and reliable approaches for the evaluation of differentiation strategies are needed.…”

Section: The Lvv Systemmentioning

confidence: 99%

Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function

et al. 2012

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Engineered recombinant viral vectors are a powerful tool for vehiculating genetic information into mammalian cells. Because of their ability to infect both dividing and non-dividing cells with high efficiency, lentiviral vectors have gained particular interest for basic research and preclinical studies in the cardiovascular field. We review here the major applications for lentiviral-vector technology in the cardiovascular field: we will discuss their use in trailing gene expression during the induction of differentiation, in protocols for the isolation of cardiac cells and in the tracking of cardiac cells after transplantation in vivo; we will also describe lentivirally-mediated gene delivery uses, such as the induction of a phenotype of interest in a target cell or the treatment of cardiovascular diseases. In addition, a section of the review will be dedicated to reprogramming approaches, focusing attention on the generation of pluripotent stem cells and on transdifferentiation, two emerging strategies for the production of cardiac myocytes from human cells and for the investigation of human diseases. Finally, in order to give a perspective on their future clinical use we will critically discuss advantages and disadvantages of lentivirus-based strategies for the treatment of cardiovascular diseases.

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Generation of Functional Murine Cardiac Myocytes From Induced Pluripotent Stem Cells

Cited by 441 publications

References 29 publications

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

Lentiviral vectors and cardiovascular diseases: a genetic tool for manipulating cardiomyocyte differentiation and function

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