Engineering liver tissue from induced pluripotent stem cells: a first step in generating new organs for transplantation?
Engineering liver tissue from induced pluripotent stem cells: a first step in generating new organs for transplantation?
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DOI：
10.1002/hep.26737
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发表时间：
2013-12
期刊：
影响因子：
13.5
通讯作者：
Duncan, Stephen A.
中科院分区：
文献类型：
--
作者：
Fox, Ira J.;Duncan, Stephen A.
用于治疗终末期器官衰竭的供体器官严重短缺，凸显了利用人类诱导多能干细胞（iPSCs）生成器官的迫切需要。尽管有许多报道描述功能性细胞分化，但没有研究成功地产生三维血管化器官，如肝脏。在这里，我们展示了通过移植体外培养的肝芽（iPSC-LBs），从人多能干细胞中产生血管化和功能性的人肝脏。特定的肝细胞（未成熟的内胚层细胞注定要追踪肝细胞的命运）通过概括内皮细胞和间充质细胞之间的有机遗传相互作用，自组织成三维iPSC-LBs。免疫染色和基因表达分析显示体外培养的iPSC-LBs与体内肝芽相似。iPSC-LB移植的人血管在48小时内与宿主血管连接，开始发挥功能。功能血管的形成刺激iPSC-LBs成熟为类似成人肝脏的组织。高代谢ipsc衍生的组织在没有受体肝脏替代的情况下具有肝脏特异性功能，如蛋白质生产和人类特异性药物代谢。此外，iPSC-LBs肠系膜移植可挽救药物致死性肝衰竭模型。据我们所知，这是第一个证明从多能干细胞产生功能性人体器官的报告。尽管将这些技术转化为患者的治疗还需要努力，但器官芽移植的概念证明为研究再生医学提供了一个有希望的新方法。
A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.
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影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.1101791108
发表时间：
2011-07-19
影响因子：
11.1
作者：
Chen, Alice A.;Thomas, David K.;Bhatia, Sangeeta N.
通讯作者：
Bhatia, Sangeeta N.
DOI：
10.1073/pnas.0908381106
发表时间：
2009-09-29
影响因子：
11.1
作者：
Stevens, K. R.;Kreutziger, K. L.;Murry, C. E.
通讯作者：
Murry, C. E.
影响因子：
46.9
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
通讯作者：
Baetge, Emmanuel E.
影响因子：
11.8
作者：
Nolan, Daniel J.;Ginsberg, Michael;Israely, Edo;Palikuqi, Brisa;Poulos, Michael G.;James, Daylon;Ding, Bi-Sen;Schachterle, William;Liu, Ying;Rosenwaks, Zev;Butler, Jason M.;Xiang, Jenny;Rafii, Arash;Shido, Koji;Rabbany, Sina Y.;Elemento, Olivier;Rafii, Shahin
通讯作者：
Rafii, Shahin