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To fabricate in vitro cell-dense, three-dimensional (3D) tumor models by employing a cell sheet technology for testing anti-cancer drug efficacy. The stratified liver tumor models were fabricated by stacking contiguous HepG2 cell sheets. Triple-layer (3L), double-layer (2L), single-layer (1L) cell sheet-based liver tumor models (CSLTMs) demonstrated 106, 96, 85% cell viability, respectively, after 3 days treatment of 10 µM doxorubicin hydrochloride (DOX), while cell viability in two-dimensional (2D) conventional culture (control) was 27%. After 7 days of DOX treatment, the viabilities of 3L, 2L, 1L, control were 24, 14, 3 and 4%, respectively. Probable explanations were blocked diffusion of DOX by the intact and multilayered structure and also hypoxia in the bottom of multilayered cell sheets. CSLTMs showed a thickness-dependent cytotoxic efficacy of DOX and greater drug resistance than the control, thereby providing useful information toward the development of improved biomimetic tumor models.

Citation

Jianing Yang, Shengjun Zhao, Yunfei Ji, Lili Zhao, Qingzhu Kong, Qing Zhang. Cell sheet-based multilayered liver tumor models for anti-cancer drug screening. Biotechnology letters. 2017 Nov 20


PMID: 29159512

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