For the first time, researchers at Michigan State University have created a miniature human heart model in the laboratory that includes all the primary heart cell types, vascular tissue, and has the functioning structure of the four heart chambers.
Cardiovascular disorders are a global health problem and heart disease is the leading cause of death in the United States and most developed countries. In the United States, heart disease accounts for a third of the mortality rate. While current technologies have provided some insights into heart disease and other cardiovascular disorders, they are limited and do not provide a complete overview of disease pathogenesis. The miniature hearts could be the solution and will serve as powerful models for a range of cardiac disorders, allowing researchers to study heart disorders and congenital heart defects with a degree of precision that has not been possible before.
The miniature hearts, named human heart organoids or hHOs, were created using a novel stem cell framework using induced pluripotent stem cells. The researchers were able to mimic embryonic and fetal developmental environments and create self-assembling 3D cell constructs that replicate the structure of the human heart and recapitulate the properties of the organ. The hHOs could be grown in just a few weeks, following the natural growth of an actual fetal heart.
“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,” said Aitor Aguirre, assistant professor of biomedical engineering at MSU’s Institute for Quantitative Health Science and Engineering, and senior author of the study. “We give the cells the instructions and they know what they have to do when all the appropriate conditions are met.”
The researchers are able to scale up the process of generating new hHOs and can create numerous hHOs simultaneously with relative ease, and relatively cheaply compared to standard labor-intensive tissue engineering approaches.
While it is possible to study congenital heart defects in animal models, studies of the human heart have been limited and rely on in vitro research or donated fetal remains, which can only approximate function and development. “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,” said Aguirre.
The funding for the study came from grants from the American Heart Association and the National Institutes of Health. You can read more about the study in the paper – Generation of Heart Organoids Modeling Early Human Cardiac Development Under Defined Conditions – a pre-print of which is available on bioRxiv. DOI: 10.1101/2020.06.25.171611.