FEK self-assembled peptide hydrogels facilitate primary hepatocytes culture and pharmacokinetics screening
文献类型：期刊论文
| 作者 | He, Ting2,3; Qiao, Shida3,4; Ma, Chen3,4; Peng, Zhaoliang3,4; Wu, Zhitao1,3,4; Ma, Chenhui3,4; Han, Li3,4; Deng, Qiangqiang3,4; Zhang, Tianwei3,4; Zhu, Yishen5 |
| 刊名 | JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
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| 出版日期 | 2022-03-18 |
| 页码 | 13 |
| ISSN号 | 1552-4973 |
| 关键词 | biliary excretion index FEFEFKFK self-assembling peptide hydrogel metabolic enzymes rat primary hepatocytes sandwich culture transporters |
| DOI | 10.1002/jbm.b.35056 |
| 通讯作者 | Zhu, Yishen(zhuyish@njtech.edu.cn) ; Pan, Guoyu(gypan@simm.ac.cn) |
| 英文摘要 | A FEFEFKFK (FEK, F, phenylalaninyl; E, glutamyl; K, lysinyl)-based self-assembling peptide hydrogel (FEK-SAPH) was developed to replace sandwich culture (SC) for improved culture of primary hepatocytes in vitro. Under neutral conditions, FEK self-assembles to form beta-sheet nanofibers, which in turn form FEK-SAPH. For the culture of rat primary hepatocytes (RPH), the use of FEK-SAPH simplified operation steps and promoted excellent cell-cell interactions while maintaining the SC-related RPH polarity trend. Compared with SC, FEK-SAPH cultured RPH for 14 days, the bile duct network was formed, the secretion of albumin and urea was improved, and the metabolic clearance rate based on cytochrome P450 (CYPs) was comparable. In FEK-SAPH culture, the expression level of the biliary efflux transporter bile salt export pump increased by 230.7%, while the biliary excretion index value of deuterium-labeled sodium taurocholate (d8-TCA) differed slightly from the SC value (72% and 77%, respectively, p = .0195). The inhibitory effect of cholestasis drugs on FEK-SAPH was significantly higher than that of SC. In FEK-SAPH, hepatoprotective drugs were more effective in antagonizing hepatotoxicity induced by lithocholic acid (LCA). FEK-SAPH cultured RPH with hepatoprotective drugs can better recover from LCA-induced damage. In summary, FEK-SAPH can be used as a substitute for SC for pharmacokinetic screening to evaluate the drug absorption, disposition, metabolism, excretion, and toxicity (ADMET) in hepatocytes. |
| WOS关键词 | IN-VITRO ; COLLAGEN SANDWICH ; LIVER-DAMAGE ; MODEL ; TRANSPORTERS ; MECHANISM ; HEPATOTOXICITY ; LOCALIZATION ; SCAFFOLDS ; SILYMARIN |
| 资助项目 | Chinese Academy of Sciences[XDA16020205] ; National Science Foundation of China[81872927] ; Jiangsu Provincial Key Research and Development Program (CN), China[BE2019736] |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000770216300001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300006]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhu, Yishen; Pan, Guoyu |
| 作者单位 | 1.Nanjing Univ Chinese Med, Nanjing, Peoples R China 2.Nanjing Tech Univ, Sch Pharmaceut Sci, Nanjing, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Nanjing Tech Univ, Coll Biotechnol & Pharmaceut Engn, Nanjing 211816, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Ting,Qiao, Shida,Ma, Chen,et al. FEK self-assembled peptide hydrogels facilitate primary hepatocytes culture and pharmacokinetics screening[J]. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS,2022:13. |
| APA | He, Ting.,Qiao, Shida.,Ma, Chen.,Peng, Zhaoliang.,Wu, Zhitao.,...&Pan, Guoyu.(2022).FEK self-assembled peptide hydrogels facilitate primary hepatocytes culture and pharmacokinetics screening.JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS,13. |
| MLA | He, Ting,et al."FEK self-assembled peptide hydrogels facilitate primary hepatocytes culture and pharmacokinetics screening".JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS (2022):13. |
入库方式： OAI收割
来源：上海药物研究所
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