HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5(+) liver stem cells.
HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5(+) liver stem cells.
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HGF/R-spondin1 通过诱导 Lgr(5) 肝干细胞拯救肝功能障碍
DOI：
10.1038/s41467-017-01341-6
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发表时间：
2017-10-27
影响因子：
16.6
通讯作者：
Zhou WJ
中科院分区：
文献类型：
--
作者：
Lin Y;Fang ZP;Liu HJ;Wang LJ;Cheng Z;Tang N;Li T;Liu T;Han HX;Cao G;Liang L;Ding YQ;Zhou WJ
通过施用可溶性分子诱导内源性成体干细胞为组织损伤修复提供了一种有利的方法，这可能是胚胎或多能干细胞衍生组织移植治疗急性器官衰竭的一种临床适用且具有成本效益的替代方案。在这里，我们证明 HGF/Rspo1 诱导肝干细胞并挽救肝功能障碍。四氯化碳治疗可促进纤维化和 Lgr5+ 肝干细胞增殖，而 Lgr5 敲低则会加剧纤维化。 HGF 与 Rspo1 联合注射可增加 Lgr5+ 肝干细胞的数量，并通过减轻纤维化来改善肝功能。我们在人肝纤维化组织中观察到 Lgr5+ 肝干细胞，一旦分离出来，这些细胞就能够形成类器官，并且用 HGF/Rspo1 治疗可促进其扩增。我们认为Lgr5+肝干细胞是肝损伤治疗的一个有价值的靶点，HGF/Rspo1可用于促进肝干细胞扩增。通过移植 ESC/iPSC 衍生组织进行器官再生是一种有前途但仍然具有挑战性的方法。林等人在这里。研究表明，化学损伤引起的肝损伤不仅会引起纤维化，还会引起 Lgr5+ 细胞扩张，而 HGF/R-spondin1 治疗可进一步促进这种扩张。
Induction of endogenous adult stem cells by administering soluble molecules provides an advantageous approach for tissue damage repair, which could be a clinically applicable and cost-effective alternative to transplantation of embryonic or pluripotent stem cell-derived tissues for the treatment of acute organ failures. Here, we show that HGF/Rspo1 induce liver stem cells and rescue liver dysfunction. Carbon tetrachloride treatment promotes both fibrosis and Lgr5+ liver stem cell proliferation, whereas Lgr5 knockdown worsens fibrosis. Injection of HGF in combination with Rspo1 increases the number of Lgr5+ liver stem cells and improves liver function by attenuating fibrosis. We observe Lgr5+ liver stem cells in human liver fibrosis tissues, and once they are isolated, these cells are able to form organoids, and treatment with HGF/Rspo1 promotes their expansion. We suggest that Lgr5+ liver stem cells represent a valuable target for liver damage treatment, and that HGF/Rspo1 can be used to promote liver stem cell expansion. Organ regeneration by transplantation of ESC/iPSC-derived tissues is a promising but still challenging approach. Here Lin et al. show that liver damage caused by a chemical insult induces not only fibrosis but also Lgr5+ cell expansion that can be further promoted by treatment with HGF/R-spondin1.
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DOI：
10.1084/jem.20101559
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Takashima S;Kadowaki M;Aoyama K;Koyama M;Oshima T;Tomizuka K;Akashi K;Teshima T
通讯作者：
Teshima T
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
8.8
作者：
Barker, Nick;Rookmaaker, Maarten B.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
64.8
作者：
Hao, Huai-Xiang;Xie, Yang;Cong, Feng
通讯作者：
Cong, Feng