Healthcare (Commonwealth Union) – Millions of people die from heart disease every year, making it the world’s biggest cause of mortality. Often referred to as the “silent killer,” it can advance without any obvious signs until a serious incident, such as a heart attack or stroke, takes place. To safeguard our health and the welfare of future generations, it is crucial to comprehend the causes, risk factors, and preventative measures for heart disease.
Heart disease is not limited to adults. Thousands of children worldwide are born with or develop severe heart diseases each year, which limit their futures and endanger their lives.
A major collaboration between QIMR Berghofer, the Murdoch Children’s Research Institute (MCRI), and The Royal Children’s Hospital is helping us understand and treat severe heart diseases—particularly those impacting children.
Research in this area is crucial as there has been an increasing number of heart diseases in much younger patients in recent years.
Researchers at QIMR Berghofer’s Cardiac Bioengineering Lab have successfully created three-dimensional, lab-grown heart tissues—called cardiac organoids—that closely resemble the structure and function of adult human heart muscle. These organoids are produced using human pluripotent stem cells, which have the capacity to become any type of cell in the body. However, when transformed into heart cells, they typically remain in an immature state, more like fetal heart tissue. This lack of maturity has made it challenging to study heart diseases that occur during childhood or adulthood.
In this study, scientists activated two essential biological signaling pathways that simulate the benefits of physical activity, which in turn helped the heart cells develop into a more mature, adult-like state. This advancement allows researchers to use the engineered tissues to test potential new medications for heart conditions. The results of this research were published in the journal Nature Cardiovascular Research.
Professor James Hudson of QIMR Berghofer stated that the small hearts may be the size of a chia seed, however they provide a platform to seek out new treatments. “There’s huge benefit to studying heart diseases in this way. Using human cardiac organoids allows us to screen many more compounds, speeding up the process of drug development.”
The scientists also simulated forms of heart disease linked to specific genetic mutations in the ryanodine, calsequestrin, and desmoplakin genes. One condition in particular—Desmoplakin cardiomyopathy—has historically been difficult to investigate, but the team succeeded in replicating major characteristics of the disorder using their newly developed lab-grown heart tissue.
According to Professor Hudson, the findings are encouraging on multiple fronts. He indicated that in the cardiac organoids, the disease triggered fibrosis (scarring) and reduced the tissue’s pumping ability—closely mirroring the symptoms seen in real patients. Professor Hudson further stated that they then trialled a novel drug, known as a ‘bromodomain and extra-terminal protein inhibitor,’ and observed an improvement in how the heart tissue functioned.
The Murdoch Children’s Research Institute and The Royal Children’s Hospital made vital contributions by conducting detailed genetic and protein-level analyses and by modelling heart disease using donated samples from the Melbourne Children’s Heart Tissue Bank.
Associate Professor Richard Mills of the MCRI indicated that the results will speed up the process of marking the specific treatments that can enhance heart function. “Our approach allows us to more accurately model childhood heart conditions, to ultimately find better treatments for some of the sickest people in our community. The collaboration with QIMR Berghofer and The Royal Children’s Hospital is accelerating progress towards these goals, and this approach has the potential to be used across a whole spectrum of childhood heart disease.”
The researchers gratefully acknowledged the support provided by the Snow Medical Research Foundation and the Novo Nordisk Foundation Center for Stem Cell Medicine.
