Engineered 3D-microtumours for personalized cancer therapy


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Nobina Mukherjee1,Prof. Hagan Bayley1
1University of Oxford

Abstract

Background

Lack of patient’s response to cancer treatment is one of healthcare’s biggest challenges. A fundamental reason for this is the cellular heterogeneity that exists within and between cancer patients. Tissue engineering can address this by forming physiologically relevant, 3D-tumour models for drug evaluation. The development of personalized therapies specifically tailored to tumour models derived from patient biopsies will revolutionize cancer treatment. 3D human tumour models will have greater predictive capability over animal models that often exhibit species-dependent drug responses. They will therefore reduce the economic and ethical costs of drug discovery.

The objective of our research is to engineer 3D-microtumours from patient biopsy-derived cells and use them as a platform to predict the treatment of individual cancer patient. 

Method

We have developed a droplet microfluidic based technique for the highly-scalable and reproducible production of microtumours from the cells of individual patients. In our most recent work, we have fabricated monodisperse, matrix protein (ECM) containing 3D-microtumours (diameter: 150 μm to 1000 μm) with high throughput (thousands of highly reproducible microtumours can be produced in 2 hours). This novel microfluidic will significantly advance the application of personalized cancer therapies.

Results

As a proof-of-principle we have engineered co-culture microtumours of human ovarian cancer cells and fibroblasts in Matrigel. In our system, structures are tailorable in size. Large microtumours are spontaneously produced by templating on the diameter of the PTFE tube. Previously, the production of large spheroids (diameter >500 μm), which are essential to study hypoxia in tumour, was only possible from small cell aggregates and took 1–2 weeks. In a first of its kind demonstration we have engineered Matrigel-containing microtumours at the production rate of 10 per second.  Cells in the 3D-microtumours show approximately 90% viability after production and can proliferate, migrate, and assume expected morphologies.

Conclusion

Our approach demonstrates the power of tissue engineering and microfluidics on being able to construct microtumour mimics from the patient biopsy and test chemotherapeutics based on individual's drug response. This time- and cost-effective, high-throughput approach will make personalized therapy part of the mainstream healthcare. This will enable a significant step towards making personalised cancer therapy accessible to all.