Scientists at Oregon Health & Science University’s Knight Cancer Institute are pioneering a new way to study cancer that could lead to faster cancer detection and more targeted treatment. It involves 3D printing cancer cells from a patient and miniature versions of organs like bones and lungs. The healthy tissue and cancer cells are placed together inside a tiny device that’s roughly the size of a thumbdrive. Scientists can then observe in real time how they interact and discover ways to halt the cancer’s spread into the healthy tissue.
Luiz Bertassoni is the director of the Precision Biofabrication Hub, which he helped launch in 2022, and a professor of oncology at OHSU. Since last year, he and his team have received more than $9 million in funding from the National Institutes of Health to advance the potential of these so-called organ-on-a-chip devices in the fight against cancer. The latest grants target an aggressive form of prostate cancer that spreads to bones and a cancer of the bone that spreads to lungs. Bertassoni joins us to talk about this new technology and the promise he thinks it holds for the roughly 40% of adults in the U.S. who will likely develop cancer at some point in their lives.
Note: The following transcript was transcribed digitally and validated for accuracy, readability and formatting by an OPB volunteer.
Dave Miller: From the Gert Boyle Studio at OPB, this is Think Out Loud. I’m Dave Miller. Scientists at Oregon Health and Science University’s Knight Cancer Institute are pioneering new ways to study cancer. Among other tools, they are 3D printing cancer cells to observe how the cells behave and respond to potential treatments.
Luiz Bertassoni is a professor of oncology at OHSU and the director of the Precision Biofabrication Hub there. He and his team received more than $9 million in federal funding in the last year for these so-called organ-on-a-chip devices, and he joins us now. It’s great to have you on Think Out Loud.
Luiz Bertassoni: Thank you for having me. It’s a great pleasure to be here.
Miller: Can you describe what you call “organs on chips?”
Bertassoni: Organs on chips are these microdevices that are made out of a transparent polymer and that we can build in a way that we can put human cells inside. [We can] basically study how these cells are interacting with one another over time, because we can keep these devices under the microscope and we can facilitate interaction of different parts of the tissue or different cells that we’re putting inside of these devices. We can basically understand biology. It’s almost like you’re putting a transparent window in the human body. You can observe as things happen, but we’re doing that in the lab.
Miller: How is what you’ve just described different than taking, say, tumor cells from a biopsy and helping them grow in a petri dish?
Bertassoni: So the idea with these organs on a chip, as we call it, is that we can leverage the technologies that were originally developed for the semiconductor industry to create these tiny microstructures that actually resemble the human body precisely. So then when we put the human cells inside of these devices, they basically take the shape of the native tissue or the native organ, and that creates a structure that is a lot more representative of the actual body, much better than just cells sitting on a dish. With that, we can actually understand what is truly happening in the body in ways that we couldn’t before.
Miller: What are the challenges of creating a realistic model of an organ or a bone, complete with blood vessels or blood vessel equivalents and nerve cells? Is there an immune system? I think of human bodies, any organism, even a very simple one, as being unbelievably complex. How do you approximate that complexity?
Bertassoni: Yeah, this is a great question and it’s exactly as you described, right? The challenge is really the complexity of the real human body. What is fascinating about this is that cells that we take out of the body are hardwired to basically reassemble or recreate those exact same structures inside of these devices. I can give you an example. If we take cells from a patient’s blood vessel, we put it inside of these devices and we culture them in the right conditions, they will reform into an actual blood vessel. And that means that we can take that structure that came from that one patient and has recreated that blood vessel, and then we can test different drugs or different therapies on that exact structure, just like as if we’re treating in the patient.
Miller: When I think about a blood vessel, I imagine those cells are growing, they’re attached to something which they recognize as the organism. So how do you even do that with your polymer?
Bertassoni: This is part of the complexity. The device itself provides the confinements that will guide the cells into the structure you’re trying to create. But then when we take the cells themselves, we basically combine them with proteins that also come from the body or from other sources, in various cell types. It doesn’t have to be just blood vessel derived cells, it can be nerve cells, it can be stem cells or cancer cells. And then when we put them together with these proteins or these structures inside of the device, if we culture them correctly, if we basically do a good job at recreating that tissue, they will essentially recreate that exact morphology and the exact dynamic of that actual tissue.
That’s what allows us to basically have a transparent window into the complexity of the human body inside of this device that is sitting under the microscope. And you get to watch as the cells reconnect and recreate the tissue. We also get to watch how they respond to treatments, different therapies and whatnot.
Miller: I could geek out for longer than I think the audience would want to hear about the mechanism here. [Laughter] But you’re getting here now to where I want to turn, which is what you can actually do with these devices. What do you see that you can do with this tool, this new model, that you couldn’t do with a petri dish or with an animal model?
Bertassoni: There’s a lot that we can do. I don’t want to discount the importance of these existing models, whether they are animal models or conventional petri dish models. We’ve learned a lot through these models and they are still very important. What this provides is a complement to that.
Essentially, because we can recreate a human-based tissue – not an animal tissue – inside of these devices, and because they are actually mimicking or recreating that complexity that you alluded to – not just pure cells on a flat dish – they’re actually recreating the entire tissue in its real complexity inside of these devices. We can actually start breaking down the interactions that define whether those treatments will work or not. For example, if I’m trying to target a particular cancer with a drug, we know now that in the patient, that drug is not only interacting exclusively with the cancer cell, it’s interacting with everything around it: the blood vessels, the immune system, the innervation.
Miller: Anybody that’s been through chemo knows that it interacts with all kinds of aspects of your life.
Bertassoni: That’s exactly right. So in these devices, we actually get to recreate that entire complexity. We actually get to see how these drugs are essentially affecting the immune system, or the innervation, or the vasculature, in addition to the cancer cells themselves. It’s more representative of a response that the patient will have.
In fact, in theory, we can actually do that in an individualized manner. We can actually get the cells from that individual patient and basically recreate the complexity of that one patient in the lab. And then, because I can do that as many times as I want, I get to test many different types of treatments and treatment combinations, and hopefully predict which one will work better for that one patient. So we call it creating a “patient avatar” in the lab. That gives us all sorts of answers that previously we couldn’t quite get with other models. There are many things that these models are actually better at providing. But there are some unique aspects that these novel models are actually much better for.
Miller: Let’s take one second away from this science to hear a little bit more about your life. You trained to be a dentist, I understand. How did you go from that to becoming a cancer researcher, a professor of oncology, and an inventor or tinkerer with these kinds of biotech gadgets?
Bertassoni: I think I’ve always been very curious and the curiosity leads to creativity. When I was training as a dentist, I was there doing treatments over and over and over in a small dental office, and I was like, “that doesn’t lead to too much creativity and curiosity.” So I started getting involved with research.
Miller: You were bored by it?
Bertassoni: Yeah, I guess that’s a good word. [Laughs]
Miller: And I guess nobody wants their dentist to be bored. I mean, mainly for your own teeth, less so for your quality of life.
Bertassoni: That’s right. So the curiosity led to lots of questioning during dental school and so on, and research is a natural path to exploring your curiosity and opening up for your creativity. And that’s where I basically became a full-time researcher. It’s a good thing that in dental school I was also exposed to a lot of basic medical training, right? We also do treat cancers, for example, in dental school, all the time – oral cancers, head and neck cancers. So it gave me a pretty solid background in human biology, physiology and things that are super important for the work that I do today.
But then I also did most of my other degrees in engineering. I remember, in some of the early training that I did, walking into a room filled with engineers. And being the dentist in the room, that was a little awkward sometimes. But I think that the curiosity really sparked some unique perspective into some of these questions. That’s what we do now in this center, we really combine engineering with basic human biology and medicine. That’s what’s so unique about it.
Miller: What kind of relationships do you have with clinicians, with frontline cancer doctors who are seeing patients?
Bertassoni: This is something that is great about the Knight Cancer Institute. We are the only comprehensive cancer center in the state of Oregon, which by definition, means that we’re interacting with clinicians virtually all the time. We actually have a very strong team of clinician scientists, and I guess I’m included in that capacity because I do have a clinical background and training as well as a research background and training. But we have clinicians that are seeing patients on a regular basis, and then they come out of the clinic and go straight into a research lab. So we get to break down these concepts and the realities of actually translating some of these basic science technologies into real world applications.
That is one of the primary goals for the Knight Cancer Institute moving forward, especially with the historic gift that we received from Phil and Penny Knight recently, where we’re really proposing to change the way cancer care is provided to Oregonians and beyond. Part of the idea there is that not only we are going to make these very world class, but also we can bring some of these unique technologies to patients, hopefully accelerate the translation. And those are some of the things that are unique about the Cancer Institute and OHSU. We get to do that and translate to the clinic.
Miller: Your recent grants will focus on cancer that spreads from prostate cells to bone, and one that goes the other direction, from bone to lungs. What challenges do bones present to cancer doctors?
Bertassoni: This is a great question. I think that every type of metastatic cancer situation – basically when cancers spread in the body – is far more complex than cancers that basically stay confined to their primary site, basically where the cancer begins. With bone specifically, it’s challenging because bone is a unique type of tissue. It’s heavily calcified, it’s rigid. If you take it out of the body and you want to study in the lab, it’s not transparent. It’s very unique. The cells actually respond to that environment very differently.
That’s the benefit of these types of devices. For example, we’re able to create, several years ago, a tissue that replicates or recreates all of the complexity of the human bone inside of these microdevices. It’s heavily calcified, it has the blood vessels, it has part of the immune compartment, it has the innervation. And then when you take the cancer cell and put [it] next to this engineered bone, we actually found out that these cancer cells are spreading to this engineered bone exactly how they do in the body. And that’s what allowed us to basically study these.
It can also happen the other way around, as you said. Cancers can begin in the bone and spread to lungs or other sites. And this other project is done in collaboration with Professor Alex Davies at OHSU. He’s an expert on osteosarcoma and lung cancer. So we’re studying both cancers that start somewhere and end up spreading to bone, but also cancers that start in the bone and end up spreading to other sites like the lung.
Miller: How might the technologies you’re talking about and working with help people who are dealing with diseases or tissue damage that does not come from cancer?
Bertassoni: This is also a very important aspect of this line of work, because by understanding how these same tissues, when they are using healthy cells, for instance, how they form, we can actually better understand general aspects of human physiology and human biology, but also how to regenerate them. Pretty much what we’re doing in these microdevices or in these models is trying to recreate those tissues – that’s what I was explaining at the very beginning. So when we understand the conditions that are appropriate for these tissues to form, that helps us understand how we would go about creating those tissues to implant in a patient that has lost, for instance, a piece of bone or has lost a piece of their lung.
So there’s a lot of overlap in the understanding of that fundamental biology. And we can really translate that in different directions, whether it’s for cancer applications or for regenerative applications. And we do both.
Miller: What’s the timeline for that latter part, the implantation of these lab-created tissues?
Bertassoni: Well, there’s a lot of it that is already hitting the clinic. It really comes down to the complexity. For example, the field of regenerative medicine has used what we call scaffolds for several years now. Those are materials that are created in the lab that, once implanted, can basically guide the cells from the patient to repopulate those areas that are lost and essentially regenerate those tissues. This happens a lot in orthopedic applications, for example, or skin regeneration. These are quite common.
Creating the entire tissue from scratch in the lab, it’s a little bit more complex. There are some regulatory hurdles to enable that. But we’re actually very close to enabling these types of applications in relatively simple tissues that are examples in the clinic … cartilage, for example, or skin, using basically engineered cells in the lab together with scaffolds that are implanted.
The real challenge is to do that to full organs. If you have liver failure, for instance, you need an entire liver. Now, we really have to go back to the lab and create an entire liver from scratch. That’s a lot more complex.
Miller: A whole organ that is very complex and can keep your system clean.
Bertassoni: And that’s where the bioprinting comes in handy. Because the bioprinting allows us to take those cells and basically give the right shape, the right anatomy, the right conditions to put those cells in the right location, in the right time, and ideally facilitate the growth of that entire organ. [The hope is] that eventually a patient can walk into a hospital and say, “Well, I actually need a brand new liver. Can you print me one?” That’s where we’re heading towards. There’s been a lot of progress in this field for the past few years.
One of the biggest challenges, in fact, was the vasculature. And we were actually one of the first groups to actually enable printing of entire blood vessels in a three-dimensional structure. That was one of the main barriers that we’re able to circumvent. Now, the challenge is how do we create entire organs with all of the things that you said at the beginning, the immune system, the innervation, the vasculature, the response, the function that they have as an actual organ? And that is one of the things that we actually spent a lot of time in our lab and in our center working on.
Miller: Luiz Bertassoni, thanks very much.
Bertassoni: Thank you so much.
Miller: Luiz Bertassoni is professor of oncology and the founding director of the Knight Cancer Institute’s Precision Biofabrication Hub at OHSU.
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