Cardiovascular Disease Models: iPSC-Derived Cardiomyocytes

Cardiovascular diseases (CVD) comprise coronary heart disease, heart failure, myocardial infarction and stroke. They are the main cause of worldwide mortality, with CVD representing 31% of global deaths in 2015.

In the UK alone, 27.4% of male deaths and 25.2% of female deaths in 2015 were a result of CVD. In spite of the similar intersex mortality rates, the risk of CVD in women is typically under-estimated. Researchers are beginning to investigate iPSC-derived cardiomyocytes from male and female donors to augment contemporary knowledge of gender-based dissimilarities and the part that they play in the development and progression of CVD.

Why is the Risk of CVD in Women Typically Under-estimated?

As it usually develops 7-10 years later in women than in men, a misconception has arisen suggesting that women are protected against CVD. This has, in turn, caused an under-recognition of CVD in women, less aggressive therapy techniques and a lower proportion of women than men in clinical trials.

Common risk factors for CVD comprise high blood pressure, high cholesterol, obesity, smoking and type II diabetes. Although these are shared between both men and women, the weighting and significance vary between them. For example, the loss of endogenous estrogen production after menopause is commonly accompanied by an increase in blood pressure, which is substantially steeper among post-menopausal women than among age-matched men.

How can iPSC-derived Cardiomyocytes Enhance Cardiovascular Disease Research?

In recent years, significant developments have been made in regards to our understanding of gender-related CVD risk factors. Researchers have utilized models of aortic aneurysm formation, atherosclerosis, myocardial injury, pressure overload, vascular injury and volume overload, in addition to the use of transgenic and knockout mouse models, to  increase understanding of female susceptibility to CVD. Although such models have generated a substantial amount of useful information, a large number have depended on the utilization of animals.

Animal studies are characterized by high costs, are not always translatable to humans, and come with ethical concerns. The utilization of iPSC-derived cardiomyocytes thus represents an efficient and biologically relevant alternative, reducing the requirement for animal studies and offering appealing cost-reductions.

The evolution of approaches to studying ion composition represents just one example of the shifting landscape of CVD research. This has provided the focal point of numerous research groups, as the modulation of ion composition has been implicated both as an anti-arrhythmic target and as a form of protection from myocardial injury.

A 2005 study by Brown et al produced infarcts (areas of dead tissue caused by a loss of blood supply) via induction of ischemia-reperfusion injury in male and female rats. Expression of the sarcolemmal ATP-sensitive potassium (KATP) channel was subsequently calculated alongside quantification of infarct size. Protein expression was highest in female rats and corresponded with smaller infarcts, encouraging the authors to indicate a possible protective role for this ion channel in females.

In a more contemporary study, published in 2017, Papp et utilized human iPSC-derived ventricular cardiomyocytes to examine the impact of estrogen on two key calcium channels. The objective of this study was to collate the results derived from rabbit hearts with equivalent human samples, during which the iPSC-derived cardiomyocytes carried out the role of healthy human heart tissue.

In females, both channels were up-regulated by estrogen, while a similar effect was not seen in males. The authors suggested that estrogen binding to its receptor might augment channel expression, promoting Ca2+ overload, and leading to an increased risk of lethal arrhythmias among women. The latter study enabled researchers to directly compare human and animal samples in the same set of experiments.

iPSC-derived Male and Female Cardiomyocytes: Applications and Benefits

iPSC-derived cardiomyocytes permit researchers to base their findings on human cellular models, which substantially reduces dependence on animal systems. These cells are optimal for utilization in cardiotoxicity testing, drug screening and drug validation, in addition to metabolism studies and electrophysiology applications.

Further possible applications comprise their use for examining the impact of menopausal hormone treatment on cardiovascular health, and to assist in understanding how medical conditions, including growth hormone deficiency, can affect cardiac function.

Watch how Axol's human iPSC-derived Ventricular Cardiomyocytes begin to beat following thawing.

Axol’s ventricular cardiomyocytes are derived from male and female donors of diverse genetic backgrounds, providing an effectual methodology for investigating gender-based divergences in terms of CVD. Axol’s cells have undergone rigorous characterization by marker expression and have also undergone functional validation. They are complemented by Axol’s expertly optimized growth media, which helps their successful culture and propagation,  in addition to unrivaled technical assistance.

About AXOL Biosciences

Axol specializes in human cell culture.

Axol produces high quality human cell products and critical reagents such as media and growth supplements. We have a passion for great science, delivering epic support and innovating future products to help our customers advance faster in their research.

Our expertise includes reprogramming cells to iPSCs and then differentiating to various cell types. We supply differentiated cells derived from healthy donors and patients of specific disease backgrounds. As a service, we also take cells provided by customers (primary or iPSC) and then do the reprogramming (when necessary) and differentiation. Clearly, by offloading the burden of generating cells, your time is freed up to focus on the research. Axol holds the necessary licenses that are required to do iPSC work.

The package wouldn't be complete without optimized media, coating solutions and other reagents. Our in-house R&D team works hard to improve on existing media and reagents as well as innovate new products for human cell culture. We also supply a growing range of human primary cells; making Axol your first port of call for your human cell culture needs.

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Last updated: Mar 13, 2020 at 10:40 AM


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