Open AccessBone marrow endothelial progenitor cells activate hepatic stellate cells and aggravate carbon tetrachloride induced liver fibrosis in mice via paracrine factors
Author(s) -
Garg Manali,
Kaur Savneet,
Banik Arpita,
Kumar Vikash,
Rastogi Archana,
Sarin Shiv K.,
Mukhopadhyay Asok,
Trehanpati Nirupma
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12355
Subject(s) - bone marrow , hepatic stellate cell , progenitor cell , cirrhosis , paracrine signalling , fibrosis , hepatic fibrosis , medicine , pathology , stem cell , andrology , chemistry , biology , microbiology and biotechnology , receptor
Objectives Bone marrow derived endothelial progenitor cells ( BM ‐ EPC s) are increased in chronic liver disease ( CLD ). Their role in hepatic fibrosis and regeneration remains an area of intense studies. We investigated the migration and secretory functions of BM ‐ EPC s in fibrotic mice liver. Materials and methods Bone marrow cells from C57 BL 6‐ GFP mice were transplanted into the femur of irradiated C57 BL 6 mice, followed by CC l 4 doses for 8 weeks, to develop hepatic fibrosis ( n = 36). Transplanted C57 BL 6 mice without CC l 4 treatment were used as controls. EPC s were analyzed in BM , blood and liver by flow cytometry and immunofluorescence. VEGF and TGF ‐β were analysed in the hepatic stellate cells ( HSC s) and BM ‐ EPC s co‐cultures using ELISA s. Results There was a significant migration of EPC s from BM to blood and to the liver ( P ≤ 0.01). Percentage of GFP + CD 31 + EPC s and collagen proportionate area was substantially increased in the liver at 4th week of CC l 4 dosage compared to the controls (19.8% vs 1.9%, P ≤ 0.05). Levels of VEGF (533.6 pg/ml) and TGF ‐β (327.44 pg/ml) also increased significantly, when HSC s were treated with the EPC conditioned medium, as compared to controls (25.66 pg/ml and 5.87 pg/ml, respectively; P ≤ 0.001). Conclusions Present findings suggest that BM ‐ EPC s migrate to the liver during CC l4‐induced liver injury and contribute to fibrosis.