The problem is that you can only get human tissues at certain times. This is why I find bone and cartilage very interesting, as certain surgical interventions enable access if you have clinical approval for them and a surgeon that is willing to work with you.
If you then use these cells to form in-vitro microphysiologial systems or organoid models, you can study the factors that are going wrong. This allows us to take the material and what we know from the pathophysiological process that we’re studying and model it in-vitro, and then dynamically monitor cellular communication at the single-cell and at the tissue level.
You need both because they're typically unique cell populations that are driving certain processes. If you only use histology or immunohistochemistry from animal models or tissue samples, it will be challenging to gain this detailed mechanistic understanding.
This is why I'm extremely fond of the 3D models.
What has your research shown are some of the underlying causes for failed tissue repair?
Dr. Bolander: This can be a patient background. Age, for instance. We know that as we age, we lose our regenerative capacity to a certain extent. This can also be affected by:
- Lifestyle
- Gender
- Genetic background
It's something that you can easily stratify when you're selecting your patient groups.You can look at certain factors and how they affect the cells and tissues’ ability to withstand stress, certain trauma indicators, or replications.
Merging biology and technology to make 3D cell models accessible
You wear two different hats: Your Assistant Professor position in Berlin and your position as Technical Staff Member at imec.
What do those positions entail, and how do they overlap or complement each other?
Dr. Bolander: I live a dream life. If you are in the area of 3D models, you know that both biology AND technology are crucial, and typically people’s focus is restricted to one of them.
Imec is one of the world-leading institutes for nanotechnology solutions with a big arm in life science and health technology. Charité, on the other hand, is one of the largest hospitals in Europe that has a heavy focus on clinical research.
The clinicians who work there are research-minded and interested in collaborating. They don't mind walking the extra mile so we can get tissue samples. They're also interested in the outcome, so we make sure that we can use the findings we produce for translational purposes so that one day we can go back to the patient.
With these two settings, I have a team that is focused on technology development and a team that is focused on the biology that can collaborate. We have meetings together so that both teams can learn from each other. This makes us strong because both groups can have their focus, but they have a natural way of meeting each other.
How do you think the requirements for working with 3D models differ between a pharmaceutical drug development setting and your regenerative medicine setting?
Dr. Bolander: I think it's very similar to the situation with biology and technology. At the moment it's two very different things. I think we are learning that biology is not so easy, so drug screening needs to be done on more complex models. Not necessarily complex 3D bioreactor systems, but even if it's just 3D aggregates or organoids, they need to represent the right compartments from physiology.
On the other hand, we also need biological models to be relevant so that we can gain enough input from different patient populations, because we know that what happens in one patient may not be the case for another.
High throughput and added complexity are needed in both cases. We need to find a match between the two aspects.
