Model Systems for Cardiovascular Regenerative Biology

Garbern, Jessica C.; Mummery, Christine L.; Lee, Richard T.

doi:10.1101/cshperspect.a014019

Cited by 32 publications

(34 citation statements)

References 174 publications

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“…It must also reproduce the pathophysiology of the human disease to be studied as accurately as possible. In this sense, HUVEC more faithfully represents human EC behavior as compared to cell lines [73]. The HUVEC model is physiologically representative of the human vascular endothelium, allowing the study of the physiological and pathological effects of different stimuli both in an isolated form, and in co-culture with other cell types, such as leukocytes and smooth muscle cells [72].…”

Section: Advantages and Disadvantages Of The Huvec Modelmentioning

confidence: 99%

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

et al. 2020

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Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this disease better, using various experimental models. The endothelium plays a crucial role in the development of CVD, since it is an interface between bloodstream components, such as monocytes and platelets, and other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from umbilical cord was first described in 1973. To date, this model is still widely used because of the high HUVEC isolation success rate, and because HUVEC are an excellent model to study a broad array of diseases, including cardiovascular and metabolic diseases. We here review the history of HUVEC isolation, the HUVEC model over time, HUVEC culture characteristics and conditions, advantages and disadvantages of this model and finally, its applications in the area of cardiovascular diseases.

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Section: Advantages and Disadvantages Of The Huvec Modelmentioning

confidence: 99%

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

et al. 2020

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“…The major limitations for the design of new drugs for HCM relate to the lack of in vitro models of human cardiac disorders that accurately reflect disease phenotypes, as well as the genomic differences between humans and the mouse, the most common genetic animal model used for the study of human cardiovascular disorders. 97 , 98 Use of scaffolds that mimic the composition, structure, and biomechanics of the native human heart, together with differentiation of pluripotent stem cells into cardiomyocytes in HCM patients, may aid a deeper understanding of the mechanisms that lead to onset of the disease, and possibly a better understanding of the genotype-phenotype correlation. 98 , 99 Moreover, these systems can be used to screen accurate therapeutic drugs for the pathology induced by particular HCM-related mutations, allowing insights into drug efficiency, safety, and mode of action.…”

Section: Therapeutics For Hypertrophic Cardiomyopathymentioning

confidence: 99%

“… 97 , 98 Use of scaffolds that mimic the composition, structure, and biomechanics of the native human heart, together with differentiation of pluripotent stem cells into cardiomyocytes in HCM patients, may aid a deeper understanding of the mechanisms that lead to onset of the disease, and possibly a better understanding of the genotype-phenotype correlation. 98 , 99 Moreover, these systems can be used to screen accurate therapeutic drugs for the pathology induced by particular HCM-related mutations, allowing insights into drug efficiency, safety, and mode of action. 99 , 100 …”

Section: Therapeutics For Hypertrophic Cardiomyopathymentioning

confidence: 99%

Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy

Roma‐Rodrigues¹,

Fernandes²

2014

TACG

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Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems.

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“…ES cell cardiomyogenesis in vitro is a key technique in studies evaluating the molecular mechanisms of cardiomyogenesis and heart development, and also in the study of embryotoxicity [1–3]. In addition the differentiated cardiomyocytes obtained from ES cells may be used as an alternative source of neonatal cardiomyocytes in studies focused on the molecular background of heart diseases.…”

Section: Introductionmentioning

confidence: 99%

The acceleration of cardiomyogenesis in embryonic stem cells in vitro by serum depletion does not increase the number of developed cardiomyocytes

Radaszkiewicz¹,

Sýkorová²,

Binó³

et al. 2017

PLoS ONE

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The differentiation of pluripotent embryonic stem (ES) cells into various lineages in vitro represents an important tool for studying the mechanisms underlying mammalian embryogenesis. It is a key technique in studies evaluating the molecular mechanisms of cardiomyogenesis and heart development and also in embryotoxicology. Herein, modest modifications of the basic protocol for ES cell differentiation into cardiomyocytes were evaluated in order to increase the yield and differentiation status of developed cardiomyocytes. Primarily, the data show that ES cell cultivation in the form of non-adherent embryoid bodies (EBs) for 5 days compared to 8 days significantly improved cardiomyogenic differentiation. This is illustrated by the appearance of beating foci in the adherent EBs layer at earlier phases of differentiation from day 10 up to day 16 and by the significantly higher expression of genes characteristic of cardiomyogenic differentiation (sarcomeric alpha actinin, myosin heavy chain alpha and beta, myosin light chain 2 and 7, and transcriptional factor Nkx2.5) in EBs cultivated under non-adherent conditions for 5 days. The ratio of cardiomyocytes per other cells was also potentiated in EBs cultivated in non-adherent conditions for only 5 days followed by cultivation in adherent serum-free culture conditions. Nevertheless, the alteration in the percentage of beating foci among these two tested cultivation conditions vanished at later phases and also did not affect the total number of cardiomyocytes determined as myosin heavy chain positive cells at the end of the differentiation process on day 20. Thus, although these modifications of the conditions of ES cells differentiation may intensify cardiomyocyte differentiation, the final count of cardiomyocytes might not change. Thus, serum depletion was identified as a key factor that intensified cardiomyogenesis. Further, the treatment of EBs with N-acetylcysteine, a reactive oxygen species scavenger, did not affect the observed increase in cardiomyogenesis under serum depleted conditions. Interestingly, a mild induction of the ventricular-like phenotype of cardiomyocytes was observed in 5-day-old EBs compared to 8-day-old EBs. Overall, these findings bring crucial information on the mechanisms of ES cells differentiation into cardiomyocytes and on the establishment of efficient protocols for the cardiomyogenic differentiation of ES cells. Further, the importance of determining the absolute number of formed cardiomyocyte-like cells per seeded pluripotent cells in contrast to the simple quantification of the ratios of cells is highlighted.

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Model Systems for Cardiovascular Regenerative Biology

Cited by 32 publications

References 174 publications

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy

The acceleration of cardiomyogenesis in embryonic stem cells in vitro by serum depletion does not increase the number of developed cardiomyocytes

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