Author: Inês Sousa Pereira
I am not the first one on this blog to talk to you about neurodegenerative diseases. In fact, our entire project is about it. These diseases have become very concerning because of the high prevalence in our society, the fact that they are very hard to diagnose and because they are still not curable.
To understand why, you need to know that most of these diseases are only 100% diagnosed post-mortem. This means that it is very difficult to obtain samples in the early stages of the disease. To study the mechanism by which the diseases appears, we need to be able to recreate them in the lab. This recreation is not only useful to unravel the biology behind the disease but also to test drugs capable of treating it.
Did you know that drug approval can take more than 15 years? To be released to the market, drugs must be successful in three main stages: in vitro models, animal models and clinical studies (studies in humans), as you can see in the image below. The truth is that this process is not only very long, but most drugs do not make it until the end phase.
Why is that? Well, let us look at the first stage. In vitro models are usually built of one single cell layer of cells cultured in a round well. As you can imagine, moving from this to a small animal like a mouse may cause discrepancies.
So, to reach a good understanding and test drugs more efficiently, we must diminish this gap. And this is where my work comes to play in our consortium. I work with the improvement of in vitro models, both of healthy and diseased brain so that the tested drugs have a more physiological outcome and better chances of success further in the process of approval.
And how can we improve in vitro models?
Well, first we can start by their architecture. A well of a plate rarely seems like a tissue or organ. Imagine a house, not all people are okay with living in a round place without other rooms, like an igloo. They may need more rooms for more people and corridors or extra rooms to communicate. Just like models do, to allow the culture of different cell types that in common culture might not survive together but if we look at the natural tissue, they are all present.
One way to achieve this is with microfluidic devices. As Clélia told you in the first post of this blog, these devices can be used to study the brain. Their architecture is tuneable in such a way that we can create different compartments for the culture of different cell types. These devices can also include mechanical forces, such as the shear stress cells feel when blood is circulating near them.
Other way to improve in vitro models is by adding a dimension. Back to our house comparison, a standard in vitro model is in 2D, like the floor of a house. Well, you cannot really live just with the floor of a house. You must have walls and filling. That is like what 3D models try to replicate. We attempt to create a material to fill the space and bring volume to the culture. This is not always easy to achieve, because the material has to be compatible with the cell culture and allow the visualization and characterization of the cells in a similar way 2D models permit. However, previous studies show cells behave more like in vivo in 3D cultures compared to 2D ones.
As a plan becomes a house, we believe we are on the right track to build more realistic models of neurodegenerative disease to better understand and treat them.
References:
Liu, Chun, et al. "Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond." Development 145.5 (2018): dev156166.
https://www.the-scientist.com/news-opinion/new-ipsc-culture-medium-promises-weekends-off-at-low-costs--66986
https://www.criver.com/products-services/research-models-services/animal-models/mice?region=3661
https://www.pinterest.pt/pin/647392515165148015/
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