Rohit Bhargava answers questions about the future of cancer research, and how scientists are utilizing new tools to diagnose and fight cancer.
What other tools would be helpful to measure the tumor microenvironment (either in concert with the 3D scaffold or separate)?
Imaging! The most critical aspect of the microenvironment is to measure the myriad molecular changes as a function of position composition of the cellular neighborhood. This cannot be done by traditional “grind-and-bind” assays because it has to have the context of space and also the element of time. The ability to take high spatial and molecular content snapshots of microenvironments will be critical. Unfortunately, such techniques are not satisfactory now. There are several groups developing the needed tools—we are developing 3D chemical imaging that will recognize cells and molecular content right here in the Beckman Institute as well. The 3D scaffolds can be ideal means to develop these needed imaging tools.
Why will it be useful to be able to make a physical 3D tumor model, rather than just a virtual one?
A virtual model cannot, today, predict all the critical changes and response to interventions that might happen in a real system. While virtual models are a great starting point, physical models are needed to make progress. Ultimately, I see them both as essential tools. The virtual model development can benefit from insight from physical models and the physical models can be improved by virtual model optimization and experiments.
What materials are used for the 3D printing?
A wide variety of materials are used! Polymers, metal powders, sugars … today, more complex printers can even print multiple materials together. Our goal was to make scaffolds on which a variety of biological systems could be developed, so we use a biocompatible sugar that is easily removed.
Why is it so challenging to create these models?
We are trying to recreate a very complex natural process. There are intricate cues in time and space over many years that form the structures we are trying to recreate, with a much smaller set of inputs and crude tools. The first step is to create the intricate scaffold that underlies biological systems. That is the advance in this work. With support from a Beckman Institute seedling grant and a graduate fellowship to an exceptional student of ours, Matt Gelber, our group has been able to develop the printer and printing methods to print scaffolds, and optimize materials and their processing. We are now making progress in controlling the removal of the scaffolds while growing biological cells around them with postdoctoral fellow Troy Comi (a chemist) and graduate student Mark Gryka (bioengineer) leading the charge. The next challenge is to ensure that the biological growth conforms to these excellent and precise scaffolds.
Do your foresee using the 3D models clinically for an individual treatment, or are they something that might be only used in a lab?
We see the challenges as first making biological systems in the laboratory and assessing their performance against existing tools and known biological behavior. Our next goal will be to use patient cells and learn about basic biological processes that may be different from person to person. Finally, with the imaging and fabrication tools and knowledge, we can proceed to clinical use on individual patients. This is a long process and we have a lot to learn. It’s wonderful to have this long-term challenge that needs so many different concepts and disciplines. Many diverse ideas need to combine and work well for this approach to succeed. It can happen in the dynamic and exciting multidisciplinary environment at the Beckman Institute!