Transcript of Claudia Zagami's TEDxVarese Youth Talk 2021
Organoids: a step towards medicine revolution
Did you know that medicine as we know it will be completely revolutionised? Are you curious to know why and how?
Let's make an imagination exercise. Let's imagine a world where medicine is a personalised matter. Let's imagine you have a condition like recurrent stomach pain and now you're trying to balance this out with some medicines that sometimes do not work. Now imagine you still have that pain and you go to get a gastroscopy done and after a couple of weeks you receive the right medication that will make you feel effectively symptom-free. That's pretty cool right?
Now imagine something more serious like a cancer. How many times have you heard about first or second line treatment failure or recurrences? What if we could know exactly which drug will be able to fight that specific tumour? What if we could also predict how that tumour will behave in the future, acting beforehand? Now imagine you are patient on an advanced waiting list hoping for a heart or a kidney to be available for a transplant. What if you could get that organ without waiting endless years for somebody else to die in a car accident and what if having that organ will not increase your risk of rejection because it might come from your own cells?
Well today it's possible to regenerate cells in vitro from your own cells making organoids. Organoids are the key for making those scenarios a reality and today I’m going to explain to you why and how. Today I'm going to explain to you why organoids have the evolutionary potential to change not only medicine but also our lives.
So what are organoids? Organoids are made of cells and they represent a miniaturised and simplified version of an organ. They are made of cells extracted from humans. They are able to self-organise in three dimensions and resemble a small organ in a dish.
I want to draw your attention to these three words that I will come back to later: 3D models, self-organised, and human-derived. I know your mind is already puzzled by some questions like “what do you mean they resemble the function of an organ?”. Well, for example, if we think about the lungs the smallest functional unit of the lung is called the alveolar sac and that allows us to exchange gas in our lungs. Lung organoids do not look like small inflating and deflating lungs on their own but rather they resemble the smallest functional part, the alveolar sac.
How do we make organoids? First of all, we take some stem cells. In our body, all the organs have stem cells and these are responsible for regenerating and repopulating the organs and allow us to live up to 100 years healthy and functional. We can extract them from many reachable tissues like our skin or our stomach through biopsies. But you can imagine that not all the organs of our body are so accessible like the brain and to create organoids of the brain we can use either embryonic stem cells or we can programme other cells lines like the skin back to embryonic stage and then back again to become any other cell type.
When we have those stem cells, we put them in a matrix that sustains them as a scaffold. We give them a cultivation cocktail which contains every factor that they will find in a real body to make them feel at home and in those conditions they expand in 3 dimensions to create organoids.
I see a lot of question marks in your eyes so I think by now I should clarify what organoids are not. Of course they are not fully functional organs. They are only the small bricks that make the organ, not the full architecture. As we can see from the image, it is clear the difference between an organoid and a real brain. They're not big enough, they're only one millimetre in size, they're not vascularised - and here I want to say “yet” - and due to the fact they are not vascularised they cannot reach the late stage of development.
Now we have defined what an organoid is and what it is not, I want to come back to the three words I asked you to remember: 3D model, self-organised and human-derived. Did you know that many of the important discoveries in medicine in the last few centuries have been done by studying immortalised or cancer cell lines or by studying animal models? Let's think about that slowly. Despite the fact that humans are actually in 3D and definitely not immortalised, I think that we did a pretty good job.
Can you see the opportunity now? Can you imagine the boost that research will get if all future studies are done in 3D from human cells that are able to self-organise in three dimensions? Those cells know where to go and why. They know how to arrange themselves in three dimensions. This is not only amazing from a scientific point of view but could also potentially tell us so much about organ development: why organs have the shape they have and how and why they lose their shape in disease.
Organoids give us the personalised therapeutic potential. We could create an avatar of a tumour or cystic fibrosis organ and test drugs on these without losing time by treating patients with the wrong therapy, alleviating pain and potentially saving lives. We could improve our drug development capability, drastically escalating our trial size which might already be a game changer for all the rare diseases that currently don't have enough participants in clinical trials. Then we could understand how a genetic defect creates a specific phenotype, fix it with gene editing and inject the right version of those organoids back into the patient.
I’m sure that all of you are amused by this technology too and you would like to quit your job tomorrow and join me in the lab to do fascinating science but unfortunately not all this biology for now is done in 3D, it’s still done mainly in 2D. That's why it's important to talk about this so that each scientist will engage with the use of 3D models.
I personally use organoids for my research. I study pre-cancerous lesions in the stomach and I’m sure that in the future we will even be able to prevent some diseases from happening, just by understanding them. I’m sure, or I hope at least, that in the not-too-distant future we will have biobanks in which health people like me can donate their own cells to create organoids for other people like we now renew blood. I’m wondering who will be able to even implement this technology to achieve even more.
I hope to have instilled in you some hope and trust in research and to have convinced you about the power of organoids for our future and our lives.