Jianing Yang1, Shengjun Zhao2, Yunfei Ji3, Lili Zhao1, Qingzhu Kong1, Qing Zhang4. 1. Department of Spine Surgery, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei, China. 2. Department of Orthopedics, Chengde Central Hospital, Chengde, 067000, Hebei, China. 3. Department of Critical Care Medicine, Chengde Central Hospital, Chengde, 067000, Hebei, China. 4. Department of Respiration Medicine, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei, China. tissuengineering@163.com.
Abstract
OBJECTIVE: To fabricate in vitro cell-dense, three-dimensional (3D) tumor models by employing a cell sheet technology for testing anti-cancer drug efficacy. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: To fabricate in vitro cell-dense, three-dimensional (3D) tumor models by employing a cell sheet technology for testing anti-cancer drug efficacy. RESULTS: 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. CONCLUSION: 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.