title: Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy.
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.
authors.affiliation: Institute 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.
authors.forename: M
authors.initials: M
authors.lastname: Astolfi
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Péant
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Lateef
authors.affiliation: Department of Engineering Physics, Polytechnique Montréal, Montreal, QC, Canada. thomas.gervais@polytmtl.ca.
authors.forename: N
authors.initials: N
authors.lastname: Rousset
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Kendall-Dupont
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Carmona
authors.affiliation: Department of Engineering Physics, Polytechnique Montréal, Montreal, QC, Canada. thomas.gervais@polytmtl.ca.
authors.forename: F
authors.initials: F
authors.lastname: Monet
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada and Department of Surgery, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Saad
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada and Division of Gynecologic Oncology, Department of Obstetrics-Gynecology, Université de Montréal, Montreal, QC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Provencher
authors.affiliation: Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada and Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: A-M
authors.initials: AM
authors.lastname: Mes-Masson
authors.affiliation: Department of Engineering Physics, Polytechnique Montréal, Montreal, QC, Canada. thomas.gervais@polytmtl.ca and Institute of Biomedical Engineering, Polytechnique Montréal, Montreal, QC, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Gervais
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005434:Flow Cytometry; D006801:Humans; D056656:Lab-On-A-Chip Devices; D051379:Mice; D042282:Microdissection; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D057285:Precision Medicine; D046509:Tissue Culture Techniques / Q000295:instrumentation*
chemical_list: D000970:Antineoplastic Agents