February 23, 2024

Australian researchers have achieved two firsts that could help the global fight against heart disease: They have created a tiny beating heart with its own vasculature, and then revealed how the vasculature affects inflammation-driven heart damage.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide.according to World Health Organization (WHO), CVD claims approximately 17.9 million lives each year. Given our aging population and the impact of lifestyle-related risk factors, mortality from cardiovascular disease is projected to rise.

CVD includes any disease that affects the heart or circulation, such as heart attack and coronary artery disease, high blood pressure, stroke, and vascular dementia. Given the prevalence of CVD, it is important that research continues to uncover new ways to prevent, diagnose, and treat this group of diseases.

Australian researchers have contributed to accelerating research in the field of heart disease by creating miniature heart organoids.

Organoids are tiny structures that mimic human organs. They are grown in the lab using human pluripotent stem cells that can be used to “reprogram” skin or blood cell production.

“Each organoid is the size of a chia seed, measuring just 1.5 millimeters (0.06 inches) in diameter, but contains 50,000 cells inside, representing the different cell types that make up the heart,” said James Hudson, corresponding author of the study.

Here, the researchers created a tiny beating organoid, which is nothing new. But, for the first time, they were able to successfully incorporate vascular cells, the cells that line blood vessels, to bring the model heart closer to replicating a real heart.

“Incorporating vascular cells into our mini-myocardium for the first time is important because we discovered that they play a key role in tissue biology,” Hudson said. “The vascular cells make the organoids function better and beat more vigorously. This really opens up our ability to better understand the heart and model disease accurately.”

The added benefit of blood vessel cells means researchers can study how they affect inflammation, which can lead to hardening of the heart. In another first, the researchers revealed the critical role of the vasculature in inflammation-driven myocardial injury.

“When we stimulated the minimyocardium to become inflamed, we found that blood vessel cells played a central role,” Hudson said. “We only saw that the tissue with the blood vessel cells stiffened. The cells sensed what was going on and changed their behavior, and we found that the cells released a factor called endothelin to mediate the stiffening.”

The researchers say this discovery, along with the use of their novel heart organoids, could lead to new treatments for heart disease.

“This is where our new system for producing vascularized heart organoids will really give us an advantage, because we will be able to advance research into new therapies more quickly,” Hudson said.

Publication of the study will help researchers around the world create their own vascularized organoids, boosting global efforts to tackle heart disease, the researchers said. In addition, they say their findings could be used to create kidney and brain organoids, accelerating research into diseases that affect these organs.

The study was published in the journal cell report, the following video from QIMR Berghofer demonstrates the novel human heart organoids in action. James Hudson, one of its creators and author of the current study, explains how the organoid was created and how it can be used.

(embed) https://www.youtube.com/watch?v=dvMLSrK1mLY (/embed)

Vascularized Cardiac Organoids Video V2

source: QIMR Berghof