Researchers develop world's first human heart cell model

October 25, 2012

Researchers at the National Heart Centre Singapore (NHCS) have successfully created a human heart cell model of arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart muscle disorder which puts one at high risk of developing life-threatening arrhythmias and sudden cardiac death. The NHCS research team discovered that key characteristics of the disease, such as abnormal "fatty changes" and altered distribution of proteins involved in cell-cell connections (called desmosomal proteins) are reproduced in the heart cells. This novel cellular model for studying the disease could help to improve understanding on how these mutations lead to arrhythmias and clinical manifestations of ARVC. The study, the first of its kind in the world, was published in the European Heart Journal, a top ranking international peer-reviewed journal, in July 2012.

The human heart cell model was developed using patient-specific induced pluripotent stem cell (iPSC) technology which converts skin samples from an ARVC patient into on a outside the body. This technique is based on the revolutionary iPSC technology of transforming into , developed by Professor Shinya Yamanaka, winner of the 2012 Nobel Prize in Physiology/Medicine. The NHCS research team has taken a step further by developing a key clinical application of the iPSC technology by replicating one's own outside the body for the study of genetic cardiovascular diseases.

Associate Professor Philip Wong, Director, Research and Development Unit, NHCS said, "For the first time, we have created a 'crystal ball' of the disease outside the body, to look into the patient's detailed and its relationship to the manifestation of disease. There would be significant opportunities now to safely study the effects of environmental factors and treatments, including gene and drug therapy, on such diseases as they do not have to be tested on patients in the first instance."

Genetic mutations in ARVC typically affect the function of desmosomes, which are structures that attach cells to one another. Desmosomes provide strength to the heart muscle and play a signalling role between neighbouring cells. Without normal desmosomes, the heart muscle cells will detach from one another and die, particularly when the heart muscle is placed under stress (such as during vigorous exercise). The damaged heart muscle is gradually replaced by fat and scar tissue. These changes also disrupt the electrical signals that control the heartbeat, which can lead to dangerous arrhythmia and .

ARVC occurs in an estimated 1 in 2,000 to 1 in 5,000 people. The disorder may be under-diagnosed as it can be difficult to detect in people with mild or no symptoms. "Although ARVC is a rare condition, it is more commonly detected in younger individuals, in their 20s and 30s, particularly in males, and is more lethal in this age group," said Dr Reginald Liew, Deputy Director, Research and Development Unit, NHCS and principal investigator of the study. Dr Liew is also an Assistant Professor with the Duke-NUS Graduate Medical School Singapore (Duke-NUS). ARVC may not have any symptoms especially in the early stages. Common symptoms if they do occur include palpitations, light-headedness, and fainting. Those with family history of sudden cardiac death are at higher risk.

The team has also been successful in using the iPSC technology to replicate other inherited heart rhythm diseases such as long QT syndrome (LQTS) and Brugada Syndrome. These diseases are caused by mutations in genes coding for proteins that control the electrical activity of the heart which can lead to ventricular arrhythmias, blackouts and sudden cardiac death.

"Our success in using iPSCs as a platform for the study of genetic cardiovascular diseases was made possible with the clear and cohesive networking between the research scientists, clinicians and bio-medical engineers. The collaborative efforts with other leading research institutions in Singapore, including Duke-NUS, NUS and A*STAR, has allowed NHCS to take a lead globally in this area and enhance Singapore's reputation as a leader in translational cardiovascular research," said Associate Professor Wong. The recognition has been followed with invitations for collaboration from other internationally recognised research centres working in this area.

The 10-member research team comprises six research scientists, two clinician scientists and two staff from the Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore. The three-year project which started in 2010, was supported with a research grant from Goh Foundation and administered through Duke-NUS.

"The next stage is for us to use this ARVC model to understand more about the disease and to specifically use such models to risk stratify patients with risk of cardiac arrhythmias. Such models will allow us to measure risk in individuals safely and tailor individual preventive programmes and treatments to patients in a more precise manner, i.e. the practice of 'stratified and personalised' medicine," said Associate Professor Wong.

Explore further: Aggregating instead of stabilizing: New insights into the mechanisms of heart disease

Related Stories

Aggregating instead of stabilizing: New insights into the mechanisms of heart disease

May 23, 2012
Malformed desmin proteins aggregate with intact proteins of the same kind, thereby triggering skeletal and cardiac muscle diseases, the desminopathies. This was discovered by researchers from the RUB Heart and Diabetes Center ...

Heart cells derived from stem cells used to study heart diseases

May 9, 2011
(PhysOrg.com) -- A research team at the University of Wisconsin School of Medicine and Public Health is the first to use heart cells derived from stem cells to specifically study certain genetic mechanisms of heart diseases.

Genetic variant increases risk of heart rhythm dysfunction, sudden death

May 30, 2012
Cardiovascular researchers at the University of Cincinnati (UC) have identified a genetic variant in a cardiac protein that can be linked to heart rhythm dysfunction.

Enzyme prevents fatal heart condition associated with athletes

May 25, 2011
Scientists have discovered an important enzyme molecule that may prevent fatal cardiac disorders associated with cardiac hypertrophy – the leading cause of sudden cardiac death in young athletes.

Genetic defects hold clues to risk for sudden cardiac death

May 10, 2011
Sudden cardiac death is always a shocking, tragic event, especially when it occurs at a young age. But, for the first time, scientists are unraveling how genetic defects can help predict the risk of dying suddenly in individuals ...

Recommended for you

Tracking effects of a food preservative on the gut microbiome

December 18, 2017
Antimicrobial compounds added to preserve food during storage are believed to be benign and non-toxic to the consumer, but there is "a critical scientific gap in understanding the potential interactions" they may have with ...

Drug found that induces apoptosis in myofibroblasts reducing fibrosis in scleroderma

December 15, 2017
(Medical Xpress)—An international team of researchers has found that the drug navitoclax can induce apoptosis (self-destruction) in myofibroblasts in mice, reducing the spread of fibrosis in scleroderma. In their paper ...

How defeating THOR could bring a hammer down on cancer

December 14, 2017
It turns out Thor, the Norse god of thunder and the Marvel superhero, has special powers when it comes to cancer too.

Researchers track muscle stem cell dynamics in response to injury and aging

December 14, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) describes the biology behind why muscle stem cells respond differently to aging or injury. The findings, published in Cell Stem Cell, ...

'Human chronobiome' study informs timing of drug delivery, precision medicine approaches

December 13, 2017
Symptoms and efficacy of medications—and indeed, many aspects of the human body itself—vary by time of day. Physicians tell patients to take their statins at bedtime because the related liver enzymes are more active during ...

Study confirms link between the number of older brothers and increased odds of being homosexual

December 12, 2017
Groundbreaking research led by a team from Brock University has further confirmed that sexual orientation for men is likely determined in the womb.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.