中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation

文献类型：期刊论文

作者Jiang, Mengmeng1,2,3; Guo, Ren2; Ai, Yan4; Wang, Gang5; Tang, Peilan6; Jia, Xiaohui2,3; He, Bingqing1,2,3; Yuan, Qianting2; Xie, Xin1,2,3,4,7
刊名JHEP REPORTS
出版日期2023-04-01
卷号5期号:4页码:11
关键词Hepatocyte transplantation Hepatocyte expansion Dedifferentiation Hepatocyte progenitor cells Small molecule compounds
DOI10.1016/j.jhepr.2023.100670
通讯作者Xie, Xin(xxie@simm.ac.cn)
英文摘要Background & Aims: Hepatocyte transplantation has emerged as a possible treatment option for end-stage liver disease. However, an important obstacle to therapeutic success is the low level of engraftment and proliferation of transplanted hepatocytes, which do not survive long enough to exert therapeutic effects. Thus, we aimed to explore the mechanisms of hepatocyte proliferation in vivo and find a way to promote the growth of transplanted hepatocytes. Methods: Hepatocyte transplantation was performed in Fah(-/-) mice to explore the mechanisms of hepatocyte proliferation in vivo. Guided by in vivo regeneration mechanisms, we identified compounds that promote hepatocyte proliferation in vitro. The in vivo effects of these compounds on transplanted hepatocytes were then evaluated. Results: The transplanted mature hepatocytes were found to dedifferentiate into hepatic progenitor cells (HPCs), which proliferate and then convert back to a mature state at the completion of liver repopulation. The combination of two small molecules Y-27632 (Y, ROCK inhibitor) and CHIR99021 (C, Wnt agonist) could convert mouse primary hepatocytes into HPCs, which could be passaged for more than 30 passages in vitro. Moreover, YC could stimulate the proliferation of transplanted hepatocytes in Fah(-/-) livers by promoting their conversion into HPCs. Netarsudil (N) and LY2090314 (L), two clinically used drugs which target the same pathways as YC, could also promote hepatocyte proliferation in vitro and in vivo, by facilitating HPC conversion. Conclusions: Our work suggests drugs promoting hepatocyte dedifferentiation may facilitate the growth of transplanted hepatocytes in vivo and may facilitate the application of hepatocyte therapy. Impact and implications: Hepatocyte transplantation may be a treatment option for patients with end-stage liver disease. However, one important obstacle to hepatocyte therapy is the low level of engraftment and proliferation of the transplanted hepatocytes. Herein, we show that small molecule compounds which promote hepatocyte proliferation in vitro by facilitating dedifferentiation, could promote the growth of transplanted hepatocytes in vivo and may facilitate the application of hepatocyte therapy. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词LIVER-INJURY ; MOUSE FIBROBLASTS ; PROGENITOR CELLS ; STEM-CELLS ; HOMEOSTASIS ; CONVERSION ; INHIBITOR ; THERAPY ; RATHER ; REPAIR
WOS研究方向Gastroenterology & Hepatology
语种英语
出版者ELSEVIER
WOS记录号WOS:001055897600001
源URL[http://119.78.100.183/handle/2S10ELR8/306995]  
专题新药研究国家重点实验室
通讯作者Xie, Xin
作者单位1.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
5.Fudan Univ, Sch Pharm, Dept Pharmaceut, Shanghai 201203, Peoples R China
6.Nanchang Univ, Sch Pharmaceut Sci, Nanchang 330006, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Jiang, Mengmeng,Guo, Ren,Ai, Yan,et al. Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation[J]. JHEP REPORTS,2023,5(4):11.
APA Jiang, Mengmeng.,Guo, Ren.,Ai, Yan.,Wang, Gang.,Tang, Peilan.,...&Xie, Xin.(2023).Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation.JHEP REPORTS,5(4),11.
MLA Jiang, Mengmeng,et al."Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation".JHEP REPORTS 5.4(2023):11.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。