Heart Attack in a Dish

Illustration of oxygen levels within an organoid and how they recreate a heart attack at the tissue level.
Low-oxygen cell culture conditions combined with human heart organoids recreate tissue-level features of a post-heart attack heart.

3D organoids give window into events immediately following a heart attack

by Christian Jones

In the U.S. someone has a heart attack every 40 seconds, but until now researchers have not had a model that fully mimics what occurs after that. Investigators from the Medical University of South Carolina and Clemson University recently reported in Nature Biomedical Engineering that they have developed human cardiac organoids that closely resemble the physiological conditions that occur during a heart attack.

The team was led by bioengineer Ying Mei, Ph.D., who holds a joint faculty position at MUSC and Clemson University. He is part of the MUSC Clemson Bioengineering program, which places Clemson bioengineers and bioengineering doctoral students on the MUSC campus so that they can interact with clinicians in need of engineering solutions. The article’s lead author, Dylan Richards, Ph.D., is a graduate of the joint program.

“We were essentially able to take that 3D complex nature of a heart attack and then downsize it into a microtissue model,” said Richards.

Organoids are three-dimensional multicellular tissues that are less than 1 millimeter in diameter. These organoids, or microtissues, function like their full-size counterparts. In this case, the heart organoids actually beat and contract as the human heart does. This model uses induced pluripotent stem cells, almost like “parent cells,” that divide and mature into several types of heart cells that interact and self-assemble to form the organoid.

Traditionally, biologists use cells in a dish or animal models, such as mice or rats, to model diseases. Cells in a dish are great for learning things at the cellular level, but it is unnatural for cells to grow in two dimensions on a flat surface. Animal models are useful in taking the next steps toward recapitulating what happens in the human body, but organoids, especially heart ones, are the closest to recreating what occurs in humans.

Because it is very difficult to obtain a sample of tissue dysfunction immediately after a heart attack occurs, most of what we know about heart attacks comes from observations made long after the initial oxygen shortage. The organoid model fills in this gap, enabling visualization immediately after the oxygen deprivation caused by a heart attack.

“This can help us to understand better how cells respond in the short term and, in turn, how that makes way for long-term damage,” said Richards.

This model also enables researchers to test whether heart drugs improve heart attack outcomes. It could also provide a way to test whether a drug that is safe in a healthy heart is also safe in a diseased one. Such information could guide physicians in prescribing drugs more appropriately in patients who had preexisting heart conditions at the time of the heart attack.

Mei intends to expand on his research by including immune cells in future studies to learn more about the role they play in restructuring heart tissue after it is damaged.

“We are not the first ones to recapitulate the cellular or even the tissue-level response. I would argue, however, that we are the first ones to recapitulate the organ-level response,” said Mei.

Editor’s note: Mei, Richards and their coauthors dedicate this work to their dear friend and coauthor Craig Beeson, Ph.D., who was lost to cancer before the publication of their article.