Luiz Bertassoni: Recreating in three dimensions the complexity of the human body

Luiz Bertassoni

Regeneration of tissues has been the research focus of Luiz Bertassoni, D.D.S., Ph.D., for more than a decade. The newest chapter of his work sees him putting his biomanufacturing technologies to work building complex models of human tissue in order to understand how cancers develop and evolve. We sat down and talked about his recent move to the Knight Cancer Institute, new uses for these technologies, and the future of his research.                    

Can you give us an overview of your research right now?

The focus of our work is to engineer complex tissue and body parts, organ-like structures and components of organs, both in order to understand how diseases evolve and also to regenerate, or reconstruct, them.

For a long time, work in my laboratory was primarily focused on the regeneration side of the story.

With the move to the Division of Oncological Sciences and CEDAR at the Knight Cancer Institute and a cancer-centric lens, we are using the biofabrication technologies we’ve developed over the last few years to create tissue models to understand cancer. Also, cancer is so often treatable now, and that has brought a need to address the effects of those treatments. In my laboratory’s work, we address some of the void left when diseased tissue is removed or destroyed in the treatment process.

With such engineered organs-on-a-chip, we can see the cells travel and metastasize before our eyes.

When we can model disease in the lab, we can more easily test approaches to treating them.

The real focus is to recreate cancer tissue in all its complexity using our tissue fabrication techniques. This will let us dissect the complexities of the cancers and understand the contribution of each one of these cells, these building blocks. It’s almost as if you had a big puzzle — and cancer is absolutely a big puzzle — and you can now separate each one of those pieces and see what each one of those pieces are doing. That’s what we’re trying to do.

We also want to know how cancers can interface with healthy tissue, so we can understand how those interactions are actually happening, how early tumors are growing, why they’re growing the way they do, and hopefully find early cures for cancer as well.

What are some advantages of using biomanufactured models for cancer research?

Traditionally, cancers have been studied by gathering cancer cells from animals or humans, putting them in a petri dish, and seeing what they do. While these methods have been very useful for many years, there are a few problems with this model: Cells may behave differently in a dish than they do in tissue, animal models don’t always translate well, and it can be very slow.

The bioengineering and biomanufacturing technologies that we will use at the Knight Cancer Precision Biofabrication hub will let us, in a way, create various copies of complex tumors, and put a window on these tissues so we can watch them evolve in real time.

Organs-on-a-chip, for example, are microchips that simulate organ structure and function. Cells, air and fluid are transported by the plastic chip’s grooves and channels in order to investigate human biology, accelerate drug discovery and enable personalized medicine.

With such engineered organs-on-a-chip, we can build an entire interconnected vascular network with patient cells and flow tumor cells in these blood capillaries to predict what they do in the body. We can see the cells travel and metastasize before our eyes. This gives a lot of power in understanding cancer biology.

The key to all of our projects is to really replicate the complexity of the human body.

What can you tell us about your projects funded by the Faculty Excellence and Innovation Award and the NCI?

Creating vascular networks

Luiz Bertassoni created a process to engineer blood vessels
Bertassoni created a process to engineer blood vessels. (OHSU/Kristyna Wentz-Graff)

The laboratory’s current project funded by the National Cancer Institute expands our work in 3D printing vascular networks. This project builds on well-established research on the organ-on-a chip, vascular-on-a-chip, and bone-in-a-dish models that we developed over the years.

We’re taking cancer cells that we know tend to metastasize to bone, and we put those cells in a vascular network created using an organ-on-a-chip model. That’s when we can actually see them travel through these engineered vascular networks and into an engineered bone-like tissue.

And again, because this is all taking place in tissues we’ve manufactured, we can actually break it down, dissect it and see what these cells are doing, which cell is doing what, when they are doing it — so you really understand that process and it really gives us a lot of power in understanding tumor biology.

At CEDAR, our plan is to apply these same technologies eventually to many cancer types. Our laboratory will be able to use these methods with other kinds of cancers, for instance with prostate or breast cancer cells.

Recreating the exact three dimensional complexity of the tumor

The project I proposed for the Faculty Excellence Award is to really enable fabrication of organs or regions of organs with single cell precision. People have done rudimentary structures, but nothing that actually replicates the position of each individual cell in the right place in the right phenotype. Our work is trying to do exactly that.

This will be taking a big step in recreating the three dimensional complexity of these tumors as they exist in the body. For that, we have to use several of these biofabrication tools, including three-dimensional printing.

We’re using three-dimensional microscopy to map the exact location of each individual tumor cell in a tissue. We can then take that map and use our bioprinters to basically recreate that entire tissue, one cell at a time. That’s truly remarkable.

Once we locate a tumor, we can replicate components of that tumor as many times as we need. We can then treat those replicas with different drugs, we can look at them in different stress conditions, we can accelerate the process of tumorigenesis and understand how that evolves.

It is a very ambitious project. And sometimes projects that are ultimately the most significant are the ones that are most challenging to get funded. Many would have considered this a pipe dream.

We thought it would take a significant amount of time to even determine the parameters that would enable us to address that problem, but we had a remarkable breakthrough and were able to solve the technical challenges in just three months. We now have a patent and are taking the first steps toward starting a company. The funding absolutely enabled us to have this big breakthrough.

That’s why it’s such a boost to get this kind of unrestricted funding. This is the kind of funding that’s so important when you have a new way to look at something or have an idea for a big leap. These are the kinds of projects that get my blood pumping.

Bertassoni holds appointments at the Cancer Early Detection Advanced Research (CEDAR) center and the Division of Oncological Sciences at the Knight Cancer Institute. He is also a faculty at the Department of Restorative Dentistry, and the Department of Biomedical Engineering.

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