Cardiovascular-related disorders are a significant global health problem. Cardiovascular disease (CVD) is the leading cause of death in developed countries, accounting for a third of the mortality rate in the United States alone. At the same time, congenital heart defects (CHD) affect less than 1 percent of newborns, making it the most common congenital disabilities in humans.
Studying cardiovascular disorders is a common problem among scientists, but now, a team of researchers from Michigan State University has created a miniature human heart model in the laboratory. For the first time in history, this mode is complete with all primary heart cell types and a functioning structure of chambers and vascular tissue.
“Here, we report the most faithful in vitro organoid model of human cardiovascular development to date using human pluripotent stem cells (hPSCs). Our protocol is highly efficient, scalable, shows high reproducibility, and is compatible with high-throughput approaches,” the researchers wrote in the paper.
The scientists believe that their model can enable them to study all kinds of cardiac disorders more accurately than before.
Appearing on the preprint server bioRxiv*, the study was funded by grants from the American Heart Association and the National Institutes of Health.
Human heart organoids (hHO)
Research on stem cells and developmental biology has made it possible to grow small pieces of tissue in the laboratory called organoids. Organoids closely resemble many organs, from the liver and brain to the kidneys.
Getting human tissue to study is difficult to obtain, but organoids provide scientists with new alternatives to study human organs and disease. They can use organoids to study the complex interactions of cells, which is not possible with other experimental models.
Human heart organoids (hHOs) are mini hearts that constitute powerful models to study all kinds of cardiac disorders. The hHOs were created by a novel stem cell framework that is based on the embryonic and fetal developmental environments.
“This process allows the stem cells to develop, basically as they would in an embryo, into the various cell types and structures present in the heart. We give the cells the instructions, and they know what they have to do when all the appropriate conditions are met,” Aitor Aguirre, the study’s senior author and assistant professor of biomedical engineering at MSU’s Institute for Quantitative Health Science and Engineering, said.
These organoids are self-assembling 3D constructs that mimic organ properties and structures, allowing scientists to study heart diseases more efficiently and more accurately at the cellular level.
“The hHOs allow higher-order interaction of distinct heart tissues for the first time and display biologically relevant physical and topographical 3D cues that closely resemble the human fetal heart. Our model constitutes a powerful novel tool for discovery and translational studies in human cardiac development and disease,” the team wrote in the paper.
Real-time analysis and observation
Further, since the organoids developed following natural cardiac embryonic development, the researchers were able to study the natural growth of an actual fetal human heart in real-time. This allows them to learn more about the heart’s structure and function.
One of the hurdles experienced by scientists in studying congenital heart defects is access to a developing heart. In the past, they study fetal heart development with the use of animal models or donated fetal remains. Now, with a mini heart that they can observe from the start of its development, it can provide more accurate information on how congenital heart defects emerge.
“Now, we can have the best of both worlds, a precise human model to study these diseases — a tiny human heart — without using fetal material or violating ethical principles. This constitutes a great step forward,” Aguirre said.
“In the lab, we are currently using heart organoids to model congenital heart disease — the most common congenital disability in humans affecting nearly 1% of the newborn population. With our heart organoids, we can study the origin of congenital heart disease and find ways to stop it,” he added.
For the research team, the study is just the first of the many experiments they will make. While their model is complex, it is far from perfect. The team plans on improving the organoid to provide a better version for future research and use.
The team said that the mini heart is not as perfect as the human heart, but they are working on it. Also, the team hopes for a broad range of applicability of the miniature hearts, enabling them to study other cardiovascular-related diseases, including chemotherapy-induced cardiotoxicity and the effects of diabetes on the developing fetal heart during pregnancy.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Israeli, Y., Gabalksi, M., Ball, K., Wasserman, A., Zou, J., Ni, G., Zhou, C., and Aguirre, A. (2020). Generation of Heart Organoids Modeling Early Human Cardiac Development Under Defined Conditions. bioRxiv. https://www.biorxiv.org/content/10.1101/2020.06.25.171611v2