Traditionally, scientists have used animal and cell models to study heart development and disease. However, researchers haven’t been able to produce a cure for congenital heart disease in part because these models are unable to capture the complexity of the human heart . Due to ethical limitations, using human embryos for these studies is out of the question.
This figure shows the heart organoid developing over 15 days. The top row is light microscope images, while the bottom two rows show two particular proteins highlighted red and blue.
Yonatan R. Lewis-Israeli et al. 2021/Nature Communications , CC BY-SA
By manipulating the ability of pluripotent stem cells to become any type of cell in the body, we guided these cells to become heart cells . The cells were able to self-assemble, replicating the main stages of human heart development during pregnancy. Our heart organoids have blood vessels and all the cell types found in the human heart, such as cardiomyocytes and pacemaker cells, which give them an edge over 2D cellular models. Furthermore, the electrophysiology and bioenergetics of these heart organoids are very similar to human embryonic hearts in ways that animal models aren’t.
Our heart organoids beat like a tiny baby’s heart, all while smaller than a grain of rice.
Pregnancy and the fetal heart
One area we’re exploring with our heart organoids is maternal and fetal cardiac health. Maternal factors such as diabetes , hypertension or even depression can increase the risk of heart disease in newborns. Studying conditions that increase the risk of congenital heart disease can prevent and reduce the incidence of cardiovascular diseases worldwide.
We can mimic these maternal environments and simulate how they influence fetal heart development with heart organoids. For example, we used heart organoids to show that diabetes, a very common condition, increases the risk of heart disease in embryos . Compared to heart organoids created in healthy conditions, mini hearts exposed to diabetic conditions developed heart abnormalities like those of human fetuses and newborns with diabetic cardiomyopathy.
Our study found that diabetes-related developmental abnormalities of the heart are likely caused by an imbalance of omega-3 fatty acids, the building blocks of cell membranes and signaling molecules. However, dietary supplementation of omega-3 fatty acids could partially restore this imbalance and prevent diabetes-induced congenital heart defects.
Drug safety during pregnancy
The drugs pregnant people take can have significant health effects on both the parent and the fetus. Medications approved for use during pregnancy are not always safe, since adequate testing is complicated . Ethical concerns limit working with biological material from people, so researchers are left with animal models that aren’t able to replicate human physiology closely enough.
Testing medications on human heart organoids allows researchers to better explore and predict potential harmful effects during pregnancy. One example is ondansetron (Zofran), a drug commonly prescribed to prevent nausea and vomiting during pregnancy. Although it has been linked with an increased risk of congenital heart disease , whether it causes the disease hasn’t been confirmed.
We showed that heart organoids exposed to ondansetron had disturbed development of ventricular cells and impaired function, similar to what’s seen in newborns exposed to ondansetron. Our findings provide data that may help update clinical guidelines on the use of the drug.
Certain medications may increase the risk of congenital heart defects.
Fiordaliso/Moment via Getty Images
Another example concerns the use of antidepressants during pregnancy, which is associated with an increased risk of congenital heart defects . Selective serotonin reuptake inhibitors, or SSRIs, the most prescribed antidepressants in pregnant people, work by increasing the availability of serotonin in the body. Serotonin is an important molecule in cardiac development. Maternal serotonin, along with antidepressants, readily pass to the embryo and alter serotonin levels in the developing heart.
In the future, we plan to expose heart organoids to antidepressants and study their effects on the incidence of congenital heart defects. The results of such research on human heart organoids may also inform recommendations for drug replacement or repurposing.
Heart organoids have the potential to help scientists more precisely study how the human heart forms and how it develops disease. In the realm of medical innovation, we believe human heart organoids grown from stem cells are the beating promise of a healthier future.
Aitor Aguirre receives funding from the NIH, AHA, Corewell-MSU Alliance Foundation and HVI.
Aleksandra Kostina and Brett Volmert do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
Source: The Conversation