Engineering mini human hearts to study pregnancy complications and birth defects

Engineering mini human hearts to study pregnancy complications and ...

How did your heart form? What triggered your first heartbeat? To this day, the mechanisms of human heart development remain elusive.

Researchers know the heart is the first organ to fully function in the growing human embryo. It begins as a simple tube that starts to pump blood by the fourth week of gestation. By the ninth week, the heart is fully formed. The heart is critical to early development because it provides essential nutrients throughout the developing fetus.

But due to its early formation, the heart is exposed for a long duration to substances a pregnant person might come into contact with, such as medications or pollutants. This may be a main reason why congenital heart disease is the most common type of birth defect in people, occurring in over 1 in 100 births worldwide.

Congenital heart defects typically require surgery to correct.

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.

To help researchers study heart development and complications in pregnancy, our team of biomedical engineers and cardiovascular scientists have spent the past several years trying to create the next best thing: mini human hearts in the lab.

Human heart organoids

Organoids are complex 3D cellular structures that replicate significant aspects of the structure and function of a specific organ in your body. While organoids are not completely synthetic, functioning organs (yet), they still possess immense power to mimic key aspects of physiology and disease in the lab.

We created our heart organoids using a type of cell called a pluripotent stem cell. Although using these cells in research used to be controversial because they were originally derived from human embryos, this is no longer a concern, as they can be produced from any adult. Pluripotent stem cells have the potential to become any type of cell in the body. This means that cells from nearly any part of your body – typically blood or skin cells – can be turned into your own stem cells to grow your own mini heart.

Grid of 24 microscopy images: the first row showing a slowly growing black sphere-like shape; the middle row a slowly growing red, blue and purple sphere; the bottom row a collection of blue circles surrounded by red

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…

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