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Nat Commun. 2017 Oct 27;8(1):1175. doi: 10.1038/s41467-017-01341-6.

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

Lin Y1,2,3, Fang ZP4, Liu HJ5, Wang LJ6, Cheng Z7, Tang N7, Li T1,2,3, Liu T1,2,3, Han HX4, Cao G8, Liang L9,10,11, Ding YQ12,13,14, Zhou WJ15,16,17.

Author information

1
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
2
Department of Pathology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
3
Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Guangzhou, Guangdong, 510515, China.
4
Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, 317000, China.
5
Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
6
Vascular Biology Research Institute, Basic Course of School, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
7
Department of Pathology, Shenzhen People's Hospital, Shenzhen, Guangdong, 515020, China.
8
Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China.
9
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. lli@smu.edu.cn.
10
Department of Pathology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. lli@smu.edu.cn.
11
Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Guangzhou, Guangdong, 510515, China. lli@smu.edu.cn.
12
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. dyqgz@126.com.
13
Department of Pathology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. dyqgz@126.com.
14
Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Guangzhou, Guangdong, 510515, China. dyqgz@126.com.
15
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. weijiezhouum@163.com.
16
Department of Pathology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China. weijiezhouum@163.com.
17
Guangdong Provincial Key Laboratory of Molecular Oncologic Pathology, Guangzhou, Guangdong, 510515, China. weijiezhouum@163.com.

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.

PMID:
29079780
PMCID:
PMC5660090
DOI:
10.1038/s41467-017-01341-6
[Indexed for MEDLINE]
Free PMC Article

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