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学科主题物理化学
Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation
Li, Na1,2; Wang, Dandan1,2; Sui, Zhigang3; Qi, Xiaoyi4; Ji, Liyun1; Wang, Xiuli3; Yang, Ling1; Yang L(杨凌)
刊名TISSUE ENGINEERING PART C-METHODS
2013-09-01
DOI10.1089/ten.tec.2012.0463
19期:9页:708-719
收录类别SCI
合作性质
文章类型Article
部门归属18
项目归属1806
产权排名待补充
WOS标题词Science & Technology ; Life Sciences & Biomedicine
资助者1,1 ; 1,1 ; 1,1 ; 1,1
类目[WOS]Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Cell Biology
研究领域[WOS]Cell Biology ; Biotechnology & Applied Microbiology
关键词[WOS]CACO-2 CELL MONOLAYERS ; EPITHELIAL-CELLS ; GROWTH-FACTOR ; PERMEABILITY ; TRANSPORT ; PREDICTION ; HUMANS ; ASSAY ; PROLIFERATION ; DISCOVERY
英文摘要Human epithelial cell culture models of monolayer Caco-2 cells have been widely employed to assess the absorption of drug molecules across intestinal mucosa. However, cautions should be taken when interpreting the conclusions from those models due to their undesirable phenotype and functionality when compared with the native intestinal tissue. In the present study, an improved, more physiologically relevant three-dimensional (3D) culture model of the intestinal mucosa was developed to study drug absorption, in which a coculture of epithelial cells, including Caco-2 cells and HT29-methotrexate cells, was indirectly seeded on a Transwell filter insert with collagen gel and stromal cells (fibroblasts and immunocytes) incorporation. This setting-up provided a compatible environment to improve the phenotype and functionality of the epithelial cells. Compared with the monolayer culture of Caco-2 cells, the reconstructed 3D model displayed more physiologically relevant characteristics evidenced by its decreased TEER value and mucus-like layer formation. A decreased expression of P-gp and an increased expression of BCRP were also observed in the current 3D culture model, leading to a changed secretory permeability of their substrates. More importantly, an improved correlation (R-2 = 0.843) was obtained between the absorptive permeability across the 3D coculture model and the human absorption fraction especially for those model compounds with moderate or high permeability. Thus, this engineered 3D coculture model presents a unique, improved opportunity to evaluate drug permeability in vitro.
语种英语
资助者1,1 ; 1,1 ; 1,1 ; 1,1
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WOS记录号WOS:000322117900005
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/119621
专题中国科学院大连化学物理研究所
通讯作者Yang L(杨凌)
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Dept Biotechnol, Dalian 116023, Peoples R China
4.Dalian Med Univ, Hosp 2, Dalian, Peoples R China
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GB/T 7714
Li, Na,Wang, Dandan,Sui, Zhigang,et al. Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation[J]. TISSUE ENGINEERING PART C-METHODS,2013,19(9):708-719.
APA Li, Na.,Wang, Dandan.,Sui, Zhigang.,Qi, Xiaoyi.,Ji, Liyun.,...&杨凌.(2013).Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation.TISSUE ENGINEERING PART C-METHODS,19(9),708-719.
MLA Li, Na,et al."Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation".TISSUE ENGINEERING PART C-METHODS 19.9(2013):708-719.
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