한빛사논문
- 조회342
UNIST
Jonghyeuk Han1, Seunggyu Jeon1, Min Kyeong Kim1, Wonwoo Jeong1, James J Yoo2,∗ and Hyun-Wook Kang1,∗
1 Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, 50, UNIST-gil, Ulju-gun, 44919 Ulsan, Republic of Korea
2 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, United States of America
∗Authors to whom any correspondence should be addressed.
Abstract
In vitro cancer models that can simulate patient-specific drug responses for personalized medicine have attracted significant attention. However, the technologies used to produce such models can only recapitulate the morphological heterogeneity of human cancer tissue. Here, we developed a novel 3D technique to bioprint an in vitro breast cancer model with patient-specific morphological features. This model can precisely mimic the cellular microstructures of heterogeneous cancer tissues and produce drug responses similar to those of human cancers. We established a bioprinting process for generating cancer cell aggregates with ductal and solid tissue microstructures that reflected the morphology of breast cancer tissues, and applied it to develop breast cancer models. The genotypic and phenotypic characteristics of the ductal and solid cancer aggregates bioprinted with human breast cancer cells (MCF7, SKBR3, MDA-MB-231) were respectively similar to those of early and advanced cancers. The bioprinted solid cancer cell aggregates showed significantly higher hypoxia (>8 times) and mesenchymal (>2–4 times) marker expressions, invasion activity (>15 times), and drug resistance than the bioprinted ductal aggregates. Co-printing the ductal and solid aggregates produced heterogeneous breast cancer tissue models that recapitulated three different stages of breast cancer tissue morphology. The bioprinted cancer tissue models representing advanced cancer were more and less resistant, respectively, to the anthracycline antibiotic doxorubicin and the hypoxia-activated prodrug tirapazamine; these were analogous to the results in human cancer. The present findings showed that cancer cell aggregates can mimic the pathological micromorphology of human breast cancer tissue and they can be bioprinted to produce breast cancer tissue in vitro that can morphologically represent the clinical stage of cancer in individual patients.
논문정보
- Research article
- 2022년 04월 (BRIC 등록일 2022-06-16)
- 국내(교신)+국외 연구진
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