Microfluidic encapsulation of tumour tissues for single cell analysis

Project Member(s): Gallego Ortega, D.

Funding or Partner Organisation: Garvan Institute of Medical Research
Garvan Institute of Medical Research

Start year: 2021

Summary: We have recently developed ALTEN, a pioneering tissue-engineering platform for anticancer drug screening directly in tumour biopsies. This biomimetic platform allows ex vivo culture of tumour tissue, preserving cell viability and diversity as well as the original tumour microenvironment. In this project we propose to use ALTEN as a rapid high-throughput method for drug screening, enabling systematic assessment of therapeutic responses using conventional techniques such as immunohistochemistry. In particular, we will use a semi-automated encapsulation system enabled by a microfluidic chip developed by Mr Guocheng Fang and Dr Hongxu Lu at UTS (Fang et al Advancer Science 2021). AIMS: We will combine ALTEN with the unprecedented capacity of scRNAseq to produce high-resolution transcriptional landscapes of drug responses in an integral tumour ecosystem to evaluate the potential of this strategy to uncover mechanisms of therapy resistance in breast cancer. Aim 1: Preclinical benchmarking of the ALTEN system with conventional patient-derived xenografts. Aim 2: Verification of the drug screening capacity of ALTEN as a precision medicine tool and validation of scRNAseq analysis as a predictive strategy. IMPACT & SIGNIFICANCE: The possibility of rapid and systematic testing of drug responses directly in patient biopsies is set to revolutionise the precision medicine arena. The unprecedented capacity of ALTEN conserving the original cell diversity and tumour ecosystem offers a new dimension to ex vivo drug testing. The combination of ALTEN with scRNAseq will expedite the application of high-resolution molecular phenotyping techniques in the clinic, advancing towards the realisation of personalised medicine, increasing diagnostic accuracy and prognostic capacity.

Publications:

Ganguly, D, Ngo, TV, Coleman, M, Sorrelle, N, Dominguez, A, Toombs, J, Schmidt, M, Mora, FV, Ortega, DG, Wellstein, A & Brekken, RA 2022, 'Abstract 3144: Pleiotrophin drives a pro-metastatic immune niche within breast tumor microenvironment', Cancer Research, vol. 82, no. 12_Supplement, pp. 3144-3144.
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FOR Codes: Medical Instruments, Cancer and Related Disorders, Biomedical instrumentation, Cancer cell biology, Instrumentation, Clinical health

Acknowledgement of Country

UTS acknowledges the Gadigal people of the Eora Nation, the Boorooberongal people of the Dharug Nation, the Bidiagal people and the Gamaygal people, upon whose ancestral lands our university stands. We would also like to pay respect to the Elders both past and present, acknowledging them as the traditional custodians of knowledge for these lands.