‘Organ-on-a-chip’ uses patient’s cancer cells in personalised model

An ‘organ-on-a-chip’ built using a patient’s cancer cells could accelerate research into a particular type of the disease and help improve precision medicine, its developers have claimed.

The prototype device was developed by Professor Ana Lleo De Nalda at Humanitas Research Hospital and Marco Rasponi from the nearby Polytechnic University of Milan.

Just a few centimetres across, the microfluidic chip has tiny channels carved into it, within which is a three-dimensional model of a bile duct cancer called cholangiocarcinoma.

“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 advancing precision medicine, since it could be potentially used as a personalised drug testing platform, helping predict patients’ response to therapies,” the researchers said.

Cholangiocarcinoma is a cancer of the liver that derives from a malignant transformation of cholangiocytes, the cells lining the bile ducts. The disease is often diagnosed at an advanced stage, because patients show very few symptoms. This is also why treatments are often ineffective, the researchers said, as many are unable to undergo surgical removal of the tumour.

“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 tumour cells and cells of the immune system, which play a key role in its progression and response to drugs,” said Professor De Nalda.

The micrometre channels in the chips were made using advanced photolithographic techniques. Cancer cells were then seeded into the chips, reproducing the tumour architecture.

To add complexity to the model and improve its reliability, researchers also seeded fibroblasts (cells forming the connective tissue), T lymphocytes (a type of immune cell), and endothelial cells (cells lining the blood vessels that feed the cancer and screen it from immune responses).

In a series of experiments, the team demonstrated that the device replicates what was observed in individual patients, both in T-cell activation, which correlates with tumour infiltration, and in therapeutic response to different drugs, based on the characteristics of cancer recurrence.

“The next steps will be to further optimise and improve the device, both as a research model and as a personalised drug-testing platform – we want to add cells of innate immune system, such as macrophages, which play an important role in tumour progression, and introduce micro-pumps that can mimic blood flow and vascularisation. 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,” the researchers said.

The work was published in the Journal of Hepatology Reports.