Micro-dissected tumor tissues on chip: an ex vivo method for drug testing and personalized therapy

被引:148
作者
Astolfi, M. [2 ,3 ,4 ]
Peant, B. [3 ,4 ]
Lateef, M. A. [3 ,4 ]
Rousset, N. [1 ]
Kendall-Dupont, J. [3 ,4 ]
Carmona, E. [3 ,4 ]
Monet, F. [1 ]
Saad, F. [3 ,4 ,5 ]
Provencher, D. [3 ,4 ,6 ]
Mes-Masson, A. -M. [3 ,4 ,7 ]
Gervais, T. [1 ,2 ,3 ,4 ]
机构
[1] Polytech Montreal, Dept Engn Phys, Montreal, PQ, Canada
[2] Polytech Montreal, Inst Biomed Engn, Montreal, PQ, Canada
[3] Ctr Hosp Univ Montreal CRCHUM, Inst Canc Montreal, Montreal, PQ, Canada
[4] Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, Montreal, PQ, Canada
[5] Univ Montreal, Fac Med, Dept Surg, Montreal, PQ H3C 3J7, Canada
[6] Univ Montreal, Dept Obstet Gynecol, Div Gynecol Oncol, Montreal, PQ, Canada
[7] Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3C 3J7, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
EPITHELIAL OVARIAN-CANCER; MULTICELLULAR SPHEROIDS; OXYGEN-CONSUMPTION; ENERGY-METABOLISM; IN-VITRO; CULTURE; GROWTH; MODEL; RATES; GLUCOSE;
D O I
10.1039/c5lc01108f
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
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 similar to 420 mu m 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.
引用
收藏
页码:312 / 325
页数:14
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