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学科主题: 物理化学
题名: Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation
作者: Li, Na1, 2;  Wang, Dandan1, 2;  Sui, Zhigang3;  Qi, Xiaoyi4;  Ji, Liyun1;  Wang, Xiuli3;  Yang, Ling1
通讯作者: 杨凌
刊名: TISSUE ENGINEERING PART C-METHODS
发表日期: 2013-09-01
DOI: 10.1089/ten.tec.2012.0463
卷: 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
类目[WOS]: Cell & Tissue Engineering ;  Biotechnology & Applied Microbiology ;  Cell Biology
资助者: 1,1
研究领域[WOS]: Cell Biology ;  Biotechnology & Applied Microbiology
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.
关键词[WOS]: CACO-2 CELL MONOLAYERS ;  EPITHELIAL-CELLS ;  GROWTH-FACTOR ;  PERMEABILITY ;  TRANSPORT ;  PREDICTION ;  HUMANS ;  ASSAY ;  PROLIFERATION ;  DISCOVERY
语种: 英语
原文出处: 查看原文
WOS记录号: WOS:000322117900005
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/119621
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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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

Recommended Citation:
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.
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