HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells

Yuan Lin, Zhe-Ping Fang, Hong-Juan Liu, Li-Jing Wang, Zhiqiang Cheng, Na Tang, Tingting Li, Tengfei Liu, Hai-Xiong Han, Guangwen Cao, Li Liang (), Yan-Qing Ding () and Wei-Jie Zhou ()
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Yuan Lin: Southern Medical University, Guangzhou
Zhe-Ping Fang: Wenzhou Medical University
Hong-Juan Liu: Southern Medical University
Li-Jing Wang: Guangdong Pharmaceutical University
Zhiqiang Cheng: Shenzhen People’s Hospital
Na Tang: Shenzhen People’s Hospital
Tingting Li: Southern Medical University, Guangzhou
Tengfei Liu: Southern Medical University, Guangzhou
Hai-Xiong Han: Wenzhou Medical University
Guangwen Cao: Second Military Medical University
Li Liang: Southern Medical University, Guangzhou
Yan-Qing Ding: Southern Medical University, Guangzhou
Wei-Jie Zhou: Southern Medical University, Guangzhou

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01341-6

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