Features of cardiomyocyte proliferation and its potential for cardiac regeneration

Amerongen, Machteld J. van; Engel, Felix B.

doi:10.1111/j.1582-4934.2008.00439.x

Cited by 116 publications

(93 citation statements)

References 116 publications

(164 reference statements)

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“…In the perinatal period, cell division ceases, cardiomyocytes withdraw from the cell cycle, and the further increase in cardiac mass is achieved through increase in cell size (hypertrophy) (1)(2)(3). The switch from hyperplastic to hypertrophic growth is characterized by extensive binucleation of cardiomyocytes.…”

mentioning

confidence: 99%

Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development

Stopp

Gründl

Fackler

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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GAS2L3 is a recently identified cytoskeleton-associated protein that interacts with actin filaments and tubulin. The in vivo function of GAS2L3 in mammals remains unknown. Here, we show that mice deficient in GAS2L3 die shortly after birth because of heart failure. Mammalian cardiomyocytes lose the ability to proliferate shortly after birth, and further increase in cardiac mass is achieved by hypertrophy. The proliferation arrest of cardiomyocytes is accompanied by binucleation through incomplete cytokinesis. We observed that GAS2L3 deficiency leads to inhibition of cardiomyocyte proliferation and to cardiomyocyte hypertrophy during embryonic development. Cardiomyocyte-specific deletion of GAS2L3 confirmed that the phenotype results from the loss of GAS2L3 in cardiomyocytes. Cardiomyocytes from Gas2l3-deficient mice exhibit increased expression of a p53-transcriptional program including the cell cycle inhibitor p21. Furthermore, loss of GAS2L3 results in premature binucleation of cardiomyocytes accompanied by unresolved midbody structures. Together these results suggest that GAS2L3 plays a specific role in cardiomyocyte cytokinesis and proliferation during heart development.binucleation | cardiomyocytes | cytokinesis | GAS2L3

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mentioning

confidence: 99%

Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development

Stopp

Gründl

Fackler

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Repair of damaged myocardium for cardiovascular applications is limited due to the low proliferative rate of cardiomyocytes in adults [162] while insufficient angiogenesis has implications in vascular disease. Scaffold-based miRNA delivery for cardiovascular-related tissue has garnered a reasonable amount of interest in recent years as it can limit the risk of undesired offtarget miRNA effects on multiple mRNAs in several different tissues and is currently a growing area of research as documented here.…”

Section: Cardiovascular Tissue Repairmentioning

confidence: 99%

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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“…To better understand molecular processes leading to myocardial diseases and to validate new cardiovascular drugs, relevant in vitro systems of human atrial and ventricular cardiomyocytes are required. However, use of primary human cardiomyocyte cultures is restricted due to the postmitotic state of this cell type [2][3][4][5]. Attempts for specific cardiomyocyte differentiation from pluripotent stem cells are still hampered by the fetal phenotype of obtained heart muscle cells [6,7].…”

Section: Introductionmentioning

confidence: 99%

Development of multiplex PCR systems for expression profiling of human cardiomyocytes induced to proliferate by lentivirus transduction of upcyte genes

George

Rödiger

Schröder

et al. 2016

JCB

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Abstract.Severe heart diseases such as myocarditis and cardiomyopathy are often characterized by progressive damages of contractile heart tissue which ultimately can lead to terminal heart failure. There is a need for relevant in vitro cultures of human cardiomyocytes to study pathogenic processes and to perform pharmacological testing of new heart drugs. By using the upcyte/EPCC (enhanced primary cell culture) approach for direct multiplication of organ-specific cells, we established proliferating human cardiomyocyte cultures derived from atrial appendages. For qualitative cardiac expression profiling we established a comprehensive set of multiplex PCR assays, selected from a panel of 32 genes, to rapidly screen changes at the transcriptional level in human ventricular and atrial cardiomyocytes. Our multiplex PCR approach revealed some donor variability of native atrial heart tissue that need to be confirmed by further studies with more samples. Our initial studies further indicated that characteristic heart muscle cell markers such as MLC-2a, MLC-2v, CHRM2, ADRB1, DES, EDRNB, Cx40 and KCNA5 were down-regulated when isolated cardiomyocytes were taken into primary cell culture. Compared to native heart tissue, proliferating atrial cardiomyocytes lacked expression of those cardiac markers but still expressed MYCD, GATA-4, Cx43, SERCA2, BNP, Tbx5, EDNRA and ACTB. Surprisingly, atrium-derived cardiomyocytes started to express NFAc4 in passage three, and cardiomyocyte marker expressions of Cx43 and BNP were even increased over cultivation time.In conclusion, our novel multiplex PCR assays should be useful for expression profiling of native heart tissues from patients with different disease conditions and for characterization of in vitro cardiomyocyte cultures.Keywords: Atrial appendages, ACTA1, ACTB ACTC1, ADRB1, ADRB2, ATP2A2, atrial fibrillation, BMP2, CHRM2, cluster analysis, DES, EDNRA, EDNRB, enhanced primary cell cultures (EPCC), GAPDH, GATA4, gene expression, GJA1, GJA5, HPRT1, KCNA5, KCNH2, multiplex PCR, MYL2, MYL7, MYOCD, NFATC4, NKX2-5, NPPA, NPPA, PLN, qPCR, reference genes, RPLP0, SCN5A, TBX5, TNNI3, TNNT2, upcyte genes, VIM Abbreviations EPCC enhanced primary cell cultures HE hematoxylin -eosin qPCR quantitative PCR 1 These authors contributed equally.

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Features of cardiomyocyte proliferation and its potential for cardiac regeneration

Cited by 116 publications

References 116 publications

Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development

Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Development of multiplex PCR systems for expression profiling of human cardiomyocytes induced to proliferate by lentivirus transduction of upcyte genes

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