Researchers at East Lansing’s Michigan State University have created a miniature human heart model in a laboratory. It includes all primary heart cell types and a functioning structure of chambers and vascular tissue.
“These mini hearts constitute incredibly powerful models in which to study all kinds of cardiac disorders with a degree of precision unseen before,” says Aitor Aguirre, the study’s senior author and assistant professor of biomedical engineering at the Institute for Quantitative Health Science and Engineering at MSU.
The human heart organoids, or hHOs, were created through a new stem cell framework that mimics the embryonic and fetal developmental environments.
“Organoids — meaning resembling an organ — are self-assembling 3-D cell constructs that recapitulate organ properties and structure to a significant extent,” says Yonatan Israeli, a graduate student in the Aguirre lab and first author of the study.
The innovation uses a bioengineering process that uses induced pluripotent stem cells, or adult cells from a patient to trigger embryonic-like heart development in a dish, generating a functional mini heart after a few weeks. The stem cells are obtained from adults.
“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,” Aguirre says. “We give the cells the instructions, and they know what they have to do when all the appropriate conditions are met.”
Because the organoids followed the natural cardiac embryonic development process, the researchers studied, in real time, the natural growth of an actual fetal human heart.
The technology allows for the creation of the hHOs simultaneously with relative ease, compared with existing tissue engineering approaches that are too expensive and labor intensive to be scalable.
One of the primary issues facing the study of fetal heart development and congenital heart defects is access to a developing heart. Researchers have been confined to the use of mammalian models, donated fetal remains, and in vitro cell research to 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,” Aguirre says.
The work is allowing the researchers to see how the heart develops.
“In the lab, we are currently using heart organoids to model congenital heart disease — the most common birth defect in humans affecting nearly 1 percent of the newborn population,” Aguirre says. “With our heart organoids, we can study the origin of congenital heart disease and find ways to stop it.”
Because the hHO is a model, it is not a perfect model of a human heart. The team is working to improve the final organoid as another avenue of research.
The study is called “Generation of Heart Organoids Modeling Early Human Development Under Defined Conditions” and was published in bioRxiv. It is available here.