Bioprinting combined with interferometry enables precision oncology

SOPHIA CHEN: Welcome to MRS Bulletin’s Materials News Podcast, providing breakthrough news & interviews with researchers on the hot topics in materials research. My name is Sophia Chen. In Alice Soragni’s lab at the University of California, Los Angeles, she and her colleagues deposit breast cancer cells in 96-well plates. You may recognize these plates as those clear rectangular containers with rows and columns of little round wells that biologists commonly use to store and culture samples, among other tasks. Soragni, an assistant professor in the department of orthopedic surgery, grows these cancer cells in each of the plate’s wells into structures known as organoids. She uses the organoids in research that could help cancer treatment. 

ALICE SORAGNI: We take the patient cells, and then we want to put them in a biological matrix that is as close as possible to like the extracellular matrix that they would encounter in the patient. We let these develop in three dimensions, and this is what we refer to as organoids.

SOPHIA CHEN: Using the organoids, Soragni has developed a technique that could help cancer patients identify effective drugs. This type of personalized treatment is known as precision oncology. Typically, precision oncology involves sequencing the patient’s tumor’s DNA, identifying the mutations leading to the cancer, and giving the patient drugs targeting those particular mutations. But Soragni says that researchers haven’t been able to develop many drugs to target specific mutations. So she is taking a different approach to identifying effective drug treatments. Soragni adds various drugs to the cells to directly to test their response to each drug, rather than sequencing the tumor.

ALICE SORAGNI: We want to take the tumor tissue in and of itself, and then basically just broadly screen drugs. So throw at it a bunch of drugs, and see what works for each and every specific tumor.

SOPHIA CHEN: They make the organoids using the technique of bioprinting, where they extrude the cells and extracellular matrix components such as proteins out of a syringe into their desired shapes. They grow the organoids in the shape of a square, where each point of the square is fixed to the edge of the circular well on the plate. The middle of the square is hollow and contains no cells. This hollow structure allows them to use the typical equipment designed for the plates to inject drugs into the wells in an automated way. Soragni says this new technique allows them to test many types of drugs efficiently and consistently.

ALICE SORAGNI: It allows us very reproducibly, to print different geometrical shapes in the 96-well format. It really allows us to use high throughput approaches to add drugs and measure viability without having to ever touch or move or having to transfer our organoids.

SOPHIA CHEN: They should also be able to screen the drugs fast enough to be useful clinically, she says.

ALICE SORAGNI: The day we get the cells from the operating room to the day we're done is less than one week.

SOPHIA CHEN: To check the drugs’ effectiveness, they measure the organoid’s mass. If the organoid shrinks, it’s a sign the drug works. To measure the cells’ mass, they use a non-invasive technique that involves shining light on the cells to monitor their response to the drug. The technique is known as interferometry. 

ALICE SORAGNI: In very simple terms, it's a method that allows us to estimate the weight of the cells.

SOPHIA CHEN: Interferometry allows them to track each organoid’s mass in real time, rather than waiting till the end of the assay. This allows them to characterize the organoid’s response to the drug in finer detail compared to measuring the mass at the end. Soragni says their group’s innovation was to combine bioprinting on the plate with interferometry, which made this high-throughput drug testing possible.

ALICE SORAGNI: We really do need to have the bioprinting because that is what technically makes interferometry on 3D structure possible.

SOPHIA CHEN: They demonstrated the high-throughput drug testing method on organoids of two breast cancer cell lines. They tested three different types of drugs, including staurosporine, which is extremely toxic, as a control. In future work, Soragni wants to see whether the organoids respond to drug treatments comparably to a real patient to the same treatment. Specifically, she wants to study how the organoids respond to drugs for treating ovarian cancer. 

ALICE SORAGNI: Ovarian cancer is a horrible disease, incredibly deadly cancer. It’s very rare, but it's very, very deadly. And there aren't really great therapies, so the outcomes are really poor for patients.

SOPHIA CHEN: She plans to monitor the effect of the most common ovarian cancer therapy on tumor organoids and compare it to the response of ovarian cancer patients. The point of that is to see if the organoids are behaving similarly to the patient and whether they can help doctors predict a patient’s response to the drug. Ultimately, she wants to use these studies to further personalize medicine, to help treat people with rare cancers. This work was published in a recent issue of Nature Communications. My name is Sophia Chen from the Materials Research Society. For more news, log onto the MRS Bulletin website at mrsbulletin.org and follow us on twitter, @MRSBulletin. Don’t miss the next episode of MRS Bulletin Materials News – subscribe now. Thank you for listening.