Feb 11
Modelling the Heart in a Dish
How heart organoids and hearts-on-chips are revolutionizing the way we study the heart
Heart disease is sadly ubiquitous — roughly 2.6 million Canadians over 20 have been diagnosed with heart disease and by the time you finish reading this post, one of these Canadians has passed away.
Fortunately, recent advances in biomedical research have made studying and finding treatments for heart disease infinitely easier than before. So join me as we enter the fascinating world of organoids — a fairly new model being used to study heart disease.
Heart Organoids: Modelling the Heart in a Dish
To start, let’s tackle what organoids are. Put simply, they’re 3D structures that model human organs in a lab. They’re also grown from stem cells; stem cells are unspecialized cell types that haven’t become a specific cell type yet. There are different types of stem cells, with the two most widely talked about being pluripotent and adult stem cells.
Pluripotent stem cells are almost entirely unspecialized, meaning they can turn into any of the 200+ cells in the human body. Adult stem cells are slightly more specialized and can’t turn into any cell.
For example, a blood stem cell can turn into a red blood cell, white blood cell, or platelet, but not an eye cell (unless a process called reprogramming is done, but that’s beyond the scope of this blog post).
It’s important to note here that these organoid models are just that — a model or a representation of a real organ. They lack some features that would make them act exactly like organs, which is why they’re not currently being used for transplants, for example. Along the same lines, the longer organoids are cultured, the less true to the human organ they become.
There are various methods for creating cardiac organoids which can have different benefits and drawbacks. However, one of the methods that is likely most true to heart development in humans (and one of the coolest) is self-assembling organoids. This is exactly what it sounds like — organoids that, when provided with the correct environment, form on their own, without scientists’ interference.
Let’s dig into some other fascinating aspects of cardiac organoids by looking at a paper by Lewis-Israeli et al.
First, the scientists working on this paper created heart organoids that included vascularization — meaning they had blood vessels — without any extra steps! This is a fairly new direction for organoids, many of which have not had blood vessels so far.
If future studies show that this vasculature is robust and closely matches what we see in the human body, this model could be used to study coronary vasculature diseases; for instance, coronary artery disease makes it hard for important blood vessels to perform their job of transporting oxygen and nutrients.
Another interesting aspect of this heart organoid model was that it formed interconnected chambers. In the human body, the heart has four chambers which are all connected and together play a critical role in moving blood around your body. What makes this point important is that it allows scientists to better study heart development and diseases in the lab. The more closely we can get lab models to resemble real organs, the more accurate our research will become (though of course this also merits ethical discussions).
The final point we’ll cover from this paper (though there are many others we didn’t get to) is how similar this model was to the fetal heart — the specific organ and developmental stage the scientists were trying to model — in terms of the breakdown of cell types.
Though we often think of heart cells as being one group, there are actually many cell types that are critical to heart development and function like cardiomyocytes (heart muscle cells) and cardiac fibroblasts (cells that support cardiomyocytes and are critical to heart damage repair). Being able to include multiple cell types in one model is once again great for accurate modelling.
The Promises and Downfalls of Organoids
We’ve already discussed some of the benefits of heart organoids but what about organoids more generally? For one, regular cell culture — which is 2D — isn’t nearly as similar to the human heart, making modelling much less accurate. As well, cell cultures usually only look at one or two cell types.
Overall, organoids are great for drug screening (studying which drugs may work best for various diseases) and disease modelling. One crazy benefit of organoids is that they allow scientists to test whether a certain drug will work for a specific patient. By taking a small biopsy from the patient, creating stem cells from that biopsy, and then creating an organoid from that, scientists can study the effects of a drug on a specific patient’s cells without possibly harming the patient!
There are, however, some drawbacks to organoids. For instance, as discussed above, the longer organoids are cultured or kept in the lab, the less true they become to the human organ, making them less effective models. And despite all of the benefits of organoids, cardiac organoids are still not as good as animal models (like mice) in terms of recapitulating heart development
Finally, an issue specific to self-assembled heart organoids is cell immaturity. The cells used resemble fetal heart cells more so than adult ones, meaning these models aren’t great for studying adult heart diseases, though they can offer lots of insight into developmental defects, for example. Plus, other types of organoids, like those that are not self-assembled, are better at modelling adult hearts.
A Step Further: Hearts-on-Chips
While heart organoids are amazing and offer a myriad of benefits for research, scientists have recently explored even newer options for studying heart disease. So let’s take a look at the heart-on-a-chip model.
Organ-on-a-chip models in general are models that include “two major components: a clear, flexible, porous membrane and living human cells, which are often derived from stem cells.” Within the flexible, porous membrane, there are small channels which allow scientists to move oxygen and blood through the cells with high precision. These models also allow scientists to precisely study how cells react to changes in the amount of blood or oxygen.
In one instance, scientists used a heart-on-a-chip to study the effects of acute hypoxia — when there are suddenly low levels of oxygen in your body — on the heart. The channels we previously discussed allowed the scientists to quickly change the amount of oxygen in the model, accurately representing what would happen in the human body.
Using this model, researchers learned exactly how the heart reacted to acute hypoxia.
All in all, both organoids and organs-on-chips offer scientists a new and highly accurate method of studying heart diseases. These models are of course not perfect but they represent a great leap forward in how we study heart disease. With greater improvement sure to come in the future, the field of cardiac organoid research has a bright future ahead — one that will hopefully help millions of patients.
To take a look at the sources for this post, click here.
About the Author
Parmin Sedigh is a 17-year-old stem cell and science communications enthusiast as well as a student researcher, based in Kingston, ON. She’s currently the VP of Communications at Eye Hope Canada. You can usually find her on her computer following her curiosity. Connect with her on LinkedIn.
