Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo.
Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo.
复制标题
永生化普通狨猴（Callithrix jacchus）肝祖细胞在体外和体内具有双潜能
DOI：
10.1038/s41421-018-0020-7
复制
发表时间：
2018
期刊：
影响因子：
33.5
通讯作者：
Yin H
中科院分区：
文献类型：
--
作者：
Guo Z;Jing R;Rao Q;Zhang L;Gao Y;Liu F;Wang X;Hui L;Yin H
普通绒猴（Callithrix jacchus）正在成为各种疾病的临床相关的非人灵长类动物模型，但受到绒猴细胞系的可用性的阻碍，这对于理解疾病发病机制和动物试验前的药物/毒理学筛选至关重要。在这里，我们描述了永生化的绒猴肝祖细胞（MHPC）的代慢病毒介导的猴病毒40大T抗原基因在胎肝多边形细胞的转移。MHPC在体外无限期增殖，没有染色体改变和端粒缩短。这些细胞具有肝祖细胞特异性基因表达谱，具有在体外和体内分化成肝细胞和胆管细胞谱系的潜力，并且还可以进行遗传修饰。重要的是，注射的MHPC用肝细胞样细胞重新填充富马酰乙酰乙酸水解酶（Fah）缺陷小鼠的损伤肝脏。MHPC还作为胆管细胞植入3，5-二乙氧羰基-1，4-二氢可力丁（DDC）诱导的胆管损伤小鼠的胆管中。MHPC提供了一种工具，使肝细胞和胆管细胞的有效衍生和遗传修饰，用于疾病建模，组织工程和药物筛选。
Common marmoset (Callithrix jacchus) is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening.
登录
查看更多内容
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
DOI：
10.1152/ajpgi.00456.2005
发表时间：
2006-05-01
影响因子：
4.5
作者：
Sicklick, JK;Li, YX;Diehl, AM
通讯作者：
Diehl, AM
使用三明治培养肝细胞模型评估早期药物发现中的胆道清除率
影响因子：
3.8
作者：
Pan, Guoyu;Boiselle, Carri;Wang, Jianling
通讯作者：
Wang, Jianling
端粒长度与 ES/iPS 细胞真实多能性的关联
影响因子：
44.1
作者：
Huang, Junjiu;Wang, Fang;Liu, Lin
通讯作者：
Liu, Lin
将人成纤维细胞直接重编程为功能性和可扩展的肝细胞
影响因子：
23.9
作者：
Huang, Pengyu;Zhang, Ludi;Hui, Lijian
通讯作者：
Hui, Lijian