A multidisciplinary team of researchers from Politecnico di Milano and Humanitas University has developed a 3D personalized model of biliary tract cancer derived from patient cells. The results were published recently in the Journal of Hepatology Reports. The model is only a few centimeters in size and can be held between two fingers, but the microchannels carved inside it have a 3D and highly faithful model of a biliary tract cancer, called cholangiocarcinoma, complete with its tumor microenvironment.
This 3D model is built starting from a sample of patient cancer cells and thus it represents a patient-specific organ-on-chip—a technology made possible only through a multidisciplinary approach that merges biomedicine, physics, and engineering.
"The ultimate goal of the device is to accelerate research on cholangiocarcinoma by providing a new laboratory model that better mimics what we observe in patients. At the same time, it will help in advancing precision medicine, since it could be potentially used as a personalized drug-testing platform, helping predict patients’ response to therapies," say Ana Lleo De Nalda, MD, PhD, full professor at Humanitas and head of the Hepatobiliary Immunopathology Lab at Humanitas Research Hospital, and Marco Rasponi, PhD, associate professor at Politecnico di Milano and head of the Laboratory of Microfluidics and Biomimetic Microsystems (MiMic Lab).
Cholangiocarcinoma: A rare and aggressive cancer
Cholangiocarcinoma is a rare cancer of the liver, which derives from a malignant transformation of cholangiocytes, the cells lining the biliary tract. Unfortunately, the disease is often diagnosed at an advanced stage, because patients show very few symptoms. This is also why treatments are often ineffective: At the time of diagnosis, only 10–30 percent of patients are eligible to undergo surgical excision of the tumor.
"Precisely because of the reduced therapeutic options and high mortality of cholangiocarcinoma, we need new in vitro models that can recapitulate the characteristics of the disease and, in particular, the interaction between tumor cells and cells of the immune system, which play a key role in its progression and response to drugs," explains De Nalda.
A platform for advancing personalized medicine
"It is a microfluidic chip a few centimeters in size. Inside the device, in the micrometer channels realized using advanced photolithographic techniques, we seeded cancer cells sampled from patients affected by cholangiocarcinoma. The cells successfully reproduced the tumor architecture in vitro,” explains Rasponi.
To add complexity to the model and improve its reliability, researchers also seeded fibroblasts, T cells, and endothelial cells. In a series of experiments, the team of researchers demonstrated that the device faithfully recapitulates what we observe in individual patients, both in terms of T-cell activation that correlates with tumor infiltration and therapeutic response to different drugs, based on the characteristics of cancer recurrence.
"The next steps will be to further optimize and improve the device, both as a research model and as a personalized drug-testing platform: We want to add cells of the innate immune system, such as macrophages, which play an important role in tumor progression, and introduce micropumps that can mimic blood flow and vascularization. We also need to test it on larger groups of patients, to confirm its ability to recapitulate the phenomena we observe in the clinical setting," conclude De Nalda and Rasponi.
- This press release was originally published on the Politecnico di Milano website