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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

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

doi

10.1038/s41467-017-01341-6

subject

Has Abstract

pub_date

2017-10-27 00:00:00

pages

1175

issue

1

issn

2041-1723

pii

10.1038/s41467-017-01341-6

journal_volume

8

pub_type

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