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Publication : HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5<sup>+</sup> liver stem cells.

First Author  Lin Y Year  2017
Journal  Nat Commun Volume  8
Issue  1 Pages  1175
PubMed ID  29079780 Mgi Jnum  J:256794
Mgi Id  MGI:6099457 Doi  10.1038/s41467-017-01341-6
Citation  Lin Y, et al. (2017) HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5(+) liver stem cells. Nat Commun 8(1):1175
abstractText  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.
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