Engineering models of early cancer: Q&A with Carolyn Schutt Ibsen

Carolyn Schutt Ibsen, Ph.D., develops biomaterials that can be controlled remotely and noninvasively using ultrasound. She and her team at OHSU are using these “energy-responsive” materials to model cancer progression, and also to guide the repair and regeneration of living tissue — applications Schutt explores at depth in a definitive new review article. Schutt is an assistant professor of biomedical engineering in the OHSU School of Medicine and a member of CEDAR, the Knight Cancer Institute’s Cancer Early Detection Advanced Research Center. She sketched out the potential of the work in a conversation with Kathryn Baker, Ph.D., presented below.

Kathryn Baker: What exactly are energy-responsive biomaterials? What medical applications are possible with these materials?

Carolyn Schutt Ibsen, Ph.D.

Carolyn Schutt Ibsen: We work with materials that have been engineered to interact with cells and biological systems in a specific way. These are materials that are biocompatible, or that support cells and their growth and keep them viable. We embed cells within hydrogel scaffolds – polymer networks resembling Jell-O – allowing the cells to interact with each other in three-dimensional space. The cells can then form structures much like they do in actual tissues. Tissue-engineered models are great for modeling disease progression and testing strategies for intervention in an in vitro fashion, but in a manner that better mimics how cells interact in the body.

The particular type of biomaterials that we develop are designed to be triggerable, meaning that at a certain time and location of your choice, you can pull the trigger to deliver various signals to the cells that are inside your biomaterial. Our recent review article, co-authored with Dr. Amy Gelmi, covers materials that are designed to influence cell behavior and fate. These rely on externally applied stimuli such as light, ultrasound, and electric and magnetic fields. Our team focuses on light and ultrasound to interact with the biomaterials and alter cellular behavior. Ultrasound is a particularly exciting trigger due to its non-invasive properties, so it allows you to manipulate materials or implanted cells deep within a scaffold. We’re interested in using ultrasound to non-invasively interact with biomaterials to cause localized payload delivery into nearby cells.

KB: And you are using these materials for modeling tumors. How do these models differ from other types of cancer models in the field?

CSI: At CEDAR, we’re using our ultrasound-responsive platform to deliver cancer-promoting factors inside of a 3D construct for modeling of early cancer. Part of what makes these models different from a lot of other 3D models is that we can locally and non-invasively manipulate the cells after they have formed structures within the biomaterial. The ultrasound passes harmlessly through the biomaterial to its focal point, where the intensity reaches a high enough level to cause interaction with the cells. It’s like we’re talking to the cells once they’ve already begun to create a more mature structure within the scaffold.

‘We want to understand how the first cells that start to show cancer-like phenotypes interact with surrounding cells in a 3D context and how they warp the behavior of healthy cells and tissue’

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KB: How closely can these stimuli-responsive models recapitulate what’s happening in the human body?

CSI: Any model system is only going to approximate what’s going on in an actual living person, but by growing these tumor models in three dimensions as opposed to 2D, we recapitulate more of the 3D architecture and interactions, such as cell-cell communication or cell-matrix interactions. These are very hard to mimic accurately in a 2D culture environment. With these 3D models we can also easily observe the cells using microscopy over time, giving us more tools to understand interactions between different cell types and crucially, between cancer-transformed cells and their surrounding healthy counterparts. These models also allow for the use of human and even patient-derived cells which we can then manipulate to explore how cells behave under different controlled perturbations.

KB: The more we learn about cancer, the more complicated the disease seems. These models seem like a great way to study a very complex disease and its interaction with the affected body. What kinds of information are you hoping to gain from these model systems? How can these models be used to improve the detection of these diseases?

CSI: We want to understand how the first cells that start to show cancer-like phenotypes interact with surrounding cells in a 3D context and how they warp the behavior of healthy cells and tissue. These interactions may happen through the production of exosomes, protein overexpression, or paracrine signaling. Because these responsive biomaterial systems that we’re developing give us a high level of control to target specific cells at specific times and locations, we can start to isolate parts of complex interactions in a complex system. Additionally, we’re interested in what sorts of biomarkers are being produced by these interactions that could be used to predict if a precancerous growth is going to become malignant and how aggressive that disease might be. We aim to not only learn about the progression of cancer, but also to find biomarkers stemming from these early stage interactions that will be useful in liquid and tissue biopsy diagnostics.

KB: What types of cancer are you focusing on?

CSI: Our current focus is on breast cancer, but we also plan to adapt our technology to other disease models. We’ve been developing this platform to remotely deliver agents that induce the expression of oncogenic proteins. We want to see how these tumor models react to a site-selected subset of tumor-transformed cells, modeling the few cells that become cancerous in an early disease state within our 3D tissue model and how these cells affect their neighbors.

KB: CEDAR has a strong engineering focus and is built around taking risks. How has the place and its culture changed your science?

CSI: CEDAR has a fantastic multi-disciplinary environment, which is critical for our work. Engineering new biomaterials technologies allows us to perturb biological systems from new angles and to expand the range of biological questions we can ask. Our team really benefits from being able to work with colleagues from different backgrounds – cancer biologists, clinicians, basic scientists – and being able to pull together the expertise of these different people to develop these techniques and drive the science forward.

 

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