CD133+ hepatic stellate cells are progenitor cells

Abstract

Hepatic stellate cells (HSC) play an important role in the development of liver fibrosis. Here, we report that HSC express the stem/progenitor cell marker CD133 and exhibit properties of progenitor cells. CD133+ HSC of rats were selected by specific antibodies and magnetic cell sorting. Selected cells displayed typical markers of HSC, endothelial progenitor cells (EPC), and monocytes. In cell culture, CD133+ HSC transformed into alpha-smooth muscle actin positive myofibroblast-like cells, whereas application of cytokines known to facilitate EPC differentiation into endothelial cells led to the formation of branched tube-like structures and induced expression of the endothelial cell markers endothelial nitric oxide synthase and vascular-endothelial cadherin. Moreover, cytokines that guide stem cells to develop hepatocytes led to the appearance of rotund cells and expression of the hepatocyte markers alpha-fetoprotein and albumin. It is concluded that CD133+ HSC are a not yet recognized progenitor cell compartment with characteristics of early EPC. Their potential to differentiate into endothelial or hepatocyte lineages suggests important functions of CD133+ HSC during liver regeneration.

The niche of stellate cells within rat liver

“…Preservation of an undifferentiated state of HSCs in the presence of parenchymal cells was indicated by the sustained CD133 and Oct4 expression. Although only a subset of HSCs can be selected by antibodies against CD133 and magnetic cell sorting, 8 indicating variable antigen abundance, CD133 and Oct4 can be stained with antibodies on all adherent HSCs that survived cell isolation without cell sorting. 11 Therefore, the expression of stem/progenitor cell markers is apparently a feature of all quiescent HSCs.…”

“…This points to a role for HSCs in liver regeneration. 8 A recent study provided additional hints that HSCs are directly involved in restoration of liver mass also in vivo. 9 Moreover, HSCs possess signaling pathways required for stem cell functions such as hedgehog and ␤-catenin-dependent Wnt signaling.…”

Helicobacter pylori accelerates hepatic fibrosis by sensitizing transforming growth factor-β1-induced inflammatory signaling

“…52 This possibility is shown in Supplementary Figures S3 and S4, wherein TGF-b1 increased Hep3B viability when accompanied by H. pylori lysates. AFP is normally expressed in fetal hepatic tissue and stem cell-derived hepatocyte-like cells, 53,54 and neoplasia of the liver 55 but is absent from adult tissue. On that score, AFP could be used as a diagnostic marker for hepatocyte differentiation or HCC.…”

“…17,56 Meanwhile, primary HSC was reported to differentiate into a hepatocyte-like cell that is round in structure and expresses AFP when treated with FGF4, HGF, bFGF, and IL-6. 54 H.pylori-induced inflammatory cytokines might lead hematopoietic progenitor cells as well as liver progenitor cells to differentiate into hepatocytes following liver damage, or abnormal proliferation of stem cells, which remains to be determined.…”

The Src family kinases: distinct functions of c-Src, Yes, and Fyn in the liver

“…Quiescent HSCs, i.e., cells that have been in culture for 24 -48 h only and do not express detectable amounts of α -smooth muscle actin, represent a hepatic stem/progenitor cell compartment in their niche (92,93) and are fairly resistant toward apoptotic cell death (94,95) . In quiescent HSC, CD95L also induces EGFR tyrosine phosphorylation and the activation of the receptor tyrosine kinase activity, but in contrast to hepatocytes, CD95L induces an EGF-dependent EGFR activation (94) .…”