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Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy
M Astolfi1, B Péant2, M A Lateef2
1Institute of Biomedical Engineering, Polytechnique Montréal, Montreal, QC, Canada and Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
Abstract:
In cancer research and personalized medicine, new tissue culture models are needed to better predict the response of patients to therapies. With a concern for the small volume of tissue typically obtained through a biopsy, we describe a method to reproducibly section live tumor tissue to submillimeter sizes. These micro-dissected tissues (MDTs) share with spheroids the advantages of being easily manipulated on-chip and kept alive for periods extending over one week, while being biologically relevant for numerous assays. At dimensions below ~420 μm in diameter, as suggested by a simple metabolite transport model and confirmed experimentally, continuous perfusion is not required to keep samples alive, considerably simplifying the technical challenges. For the long-term culture of MDTs, we describe a simple microfluidic platform that can reliably trap samples in a low shear stress environment. We report the analysis of MDT viability for eight different types of tissues (four mouse xenografts derived from human cancer cell lines, three from ovarian and prostate cancer patients, and one from a patient with benign prostatic hyperplasia) analyzed by both confocal microscopy and flow cytometry over an 8-day incubation period. Finally, we provide a proof of principle for chemosensitivity testing of human tissue from a cancer patient performed using the described MDT chip method. This technology has the potential to improve treatment success rates by identifying potential responders earlier during the course of treatment and providing opportunities for direct drug testing on patient tissues in early drug development stages.
Insights
Researchers developed micro-dissected tissues (MDTs) for cancer research. This new method allows live tumor tissue culture, improving personalized medicine and drug testing for better treatment outcomes.
Area of Science:
- Oncology
- Biotechnology
- Personalized Medicine
Background:
- Accurate prediction of patient response to cancer therapies is crucial.
- Biopsied tissue volume is often limited, posing challenges for traditional culture models.
- Novel tissue culture models are needed to bridge the gap between preclinical research and clinical application.
Purpose of the Study:
- To develop a method for culturing small, viable tumor tissue samples for improved cancer research.
- To establish a microfluidic platform for long-term culture and analysis of micro-dissected tissues (MDTs).
- To demonstrate the utility of MDTs for chemosensitivity testing and personalized medicine.
Main Methods:
- Reproducible sectioning of live tumor tissue into submillimeter micro-dissected tissues (MDTs).
- Utilizing a microfluidic platform for low shear stress, long-term culture of MDTs (up to 8 days).
- Assessing MDT viability using confocal microscopy and flow cytometry across diverse tissue types.
Main Results:
- MDTs remained viable for over a week without continuous perfusion, simplifying culture requirements.
- Successful culture and viability analysis were performed on eight different tissue types, including patient-derived xenografts and primary tumors.
- Proof-of-principle for chemosensitivity testing on patient-derived MDTs was successfully demonstrated.
Conclusions:
- Micro-dissected tissues (MDTs) offer a biologically relevant, easily manipulated, and viable model for cancer research.
- The described microfluidic platform facilitates long-term culture and analysis of MDTs, supporting personalized medicine approaches.
- MDT technology holds potential for early identification of treatment responders and direct drug testing on patient tissues.
