Long-term culture of genome-stable bipotent stem cells from adult human liver.
Long-term culture of genome-stable bipotent stem cells from adult human liver.
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DOI：
10.1016/j.cell.2014.11.050
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发表时间：
2015-01-15
期刊：
影响因子：
64.5
通讯作者：
Clevers H
中科院分区：
文献类型：
--
作者：
Huch M;Gehart H;van Boxtel R;Hamer K;Blokzijl F;Verstegen MM;Ellis E;van Wenum M;Fuchs SA;de Ligt J;van de Wetering M;Sasaki N;Boers SJ;Kemperman H;de Jonge J;Ijzermans JN;Nieuwenhuis EE;Hoekstra R;Strom S;Vries RR;van der Laan LJ;Cuppen E;Clevers H
尽管人类肝脏具有巨大的复制潜力，但目前还没有可用于维持肝细胞体外复制和/或功能的培养系统。我们之前已经表明，单个小鼠Lgr 5+肝干细胞可以在体外扩增为上皮类器官，并且可以在体外和体内分化为功能性肝细胞。我们现在描述的条件允许长期扩增成人胆管衍生的双能祖细胞从人肝脏。扩增的细胞在染色体和结构水平上高度稳定，而单碱基变化的发生率非常低。这些细胞可以在体外和体内移植后容易地转化为功能性肝细胞。来自α1-抗胰蛋白酶缺乏症和Alagille综合征患者的类器官反映了体内病理学。原代成体肝干细胞的克隆长期扩增为疾病建模、毒理学研究、再生医学和基因治疗开辟了实验途径。长期人类肝脏类器官培养物的建立人类肝脏干细胞在长期扩增后保持遗传稳定性肝脏类器官培养物在体外和体内分化为功能性肝细胞来源于患有遗传疾病的患者的类器官体外肝病模型允许人类肝脏长期扩增的培养系统可用于模拟和研究各种人类疾病。
Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. Establishment of a long-term human liver organoid culture Human liver stem cells retain genetic stability after long-term expansion Liver organoid cultures differentiate to functional hepatocytes in vitro and in vivo Organoids derived from patients with genetic disorders model liver disease in vitro A culture system that allows long-term expansion of human liver can be used to model and study various human diseases.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
10.5
作者：
Dorrell, Craig;Erker, Laura;Grompe, Markus
通讯作者：
Grompe, Markus
DOI：
10.1016/j.biocel.2008.02.008
发表时间：
2008-01-01
影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
Alpini, G
影响因子：
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作者：
Choi TY;Ninov N;Stainier DY;Shin D
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