Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.
Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.
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DOI：
10.1016/j.biocel.2012.01.002
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发表时间：
2012-04
影响因子：
4
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
He, Zhi-Ying;Deng, Li;Li, Yang-Fang;Xiang, Dao;Hu, Jun-Kai;Chen, Yuan-Xiao;Wang, Min-Jun;Chen, Fei;Liu, Chang-Cheng;Li, Wen-Lin;Zi, Xiao-Yuan;Wu, Xia;Li, Guang-Peng;Wangensteen, Kirk J.;Hu, Yi-Ping;Wang, Xin
胚胎干细胞来源的肝细胞虽然具有移植和再增殖的能力，但其体内肝功能的研究尚不多见。我们的目的是确定在富马酰乙酰乙酸水解酶敲除（Fah−/−）小鼠中连续肝脏重建后ES细胞衍生的肝细胞的代谢功能和治疗作用。使用两种经常报道的方法通过ES细胞的肝分化获得白蛋白表达（Alb+）细胞。移植后，在Fah−/−小鼠受体中发现了不同水平的肝脏再生。发现FAH表达（FAH+）肝细胞为单个细胞或具有多个肝细胞的结节。连续移植后，再移植的FAH+肝细胞重新填充的肝脏比例显著增加。ES细胞衍生的FAH+肝细胞在同质结节中被发现，并纠正了Fah-/-受体的肝脏代谢紊乱，并挽救了他们的死亡。ES细胞源性肝细胞在体内外均具有正常的核型、肝细胞形态和代谢功能。总之，ES细胞源性肝细胞能够在连续移植后进行肝脏重建和纠正代谢缺陷。我们的研究结果是一个重要的证据，以支持未来的临床应用ES细胞来源的肝细胞在治疗肝脏疾病。
Although embryonic stem (ES) cell-derived hepatocytes have the capacity for liver engraftment and repopulation, their in vivo hepatic function has not been analyzed yet. We aimed to determine the metabolic function and therapeutic action of ES cell-derived hepatocytes after serial liver repopulations in fumaryl acetoacetate hydrolase knockout (Fah−/−) mice. Albumin expressing (Alb+) cells were obtained by hepatic differentiation of ES cells using two frequently reported methods. After transplantation, variable levels of liver repopulation were found in Fah−/− mice recipients. FAH expressing (FAH+) hepatocytes were found either as single cells or as nodules with multiple hepatocytes. After serial transplantation, the proportion of the liver that was repopulated by the re-transplanted FAH+ hepatocytes increased significantly. ES cell-derived FAH+ hepatocytes were found in homogenous nodules and corrected the liver metabolic disorder of Fah−/− recipients and rescued them from death. ES cell-derived hepatocytes had normal karyotype, hepatocytic morphology and metabolic function both in vitro and in vivo. In conclusion, ES cell-derived hepatocytes were capable of liver repopulation and correction of metabolic defects after serial transplantation. Our results are an important piece of evidence to support future clinical applications of ES cell-derived hepatocytes in treating liver diseases.
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影响因子：
13.5
作者：
Heo, Jeonghoon;Factor, Valentina M.;Thorgeirsson, Snorri S.
通讯作者：
Thorgeirsson, Snorri S.
影响因子：
46.9
作者：
Gouon-Evans, Valerie;Boussemart, Lise;Keller, Gordon
通讯作者：
Keller, Gordon
影响因子：
6.2
作者：
Kumashiro, Y;Asahina, K;Teraoka, H
通讯作者：
Teraoka, H
影响因子：
3.3
作者：
Sharma, Amar Deep;Cantz, Tobias;Ott, Michael
通讯作者：
Ott, Michael
影响因子：
46.9
作者：
Soto-Gutierrez, Alejandro;Kobayashi, Naoya;Fox, Ira J.
通讯作者：
Fox, Ira J.