title: [Insulin-like growth factor-1-mediated paracrine pro-proliferative effect of bone marrow mesenchymal stem cells on injured L02 hepatocytes].
abstract: OBJECTIVE
  To explore the therapeutic effect of bone marrow mesenchymal stem cells (BM-MSCs) on injured hepatocytes mediated by paracrine mechanisms and to investigate the potential molecular mechanism of this action.
  
  
  METHODS
  A contact-independent model of aberrant hepatic microenvironment was established by co-culturing BM-MSCs with D-galactosamine (D-GalN)-injured human L02 hepatic cells using a transwell assay platform. Secreted levels of insulin-like growth factor-1 (IGF-1) were measured by enzyme-linked immunosorbent assay of the co-culture supernatant. Expression of the IGF-1 receptor (IGF-1R) was assessed by Western blot. The effect of exogenous IGF-1 on proliferation of D-GalN-injured L02 cells was examined by MTT assay.
  
  
  RESULTS
  Upon co-culture, BM-MSCs promoted proliferation of D-GalN-injured L02 cells in a contact-independent manner (absorbance values of at 24 h: 0.36+/-0.08, 48 h: 0.52+/-0.06, and 96 h: 0.68+/-0.06; vs. uninjured cells t = 2.493, 3.116, and 2.285, respectively; all P less than 0.05). Robust expression of IGF-1 was identified in the supernatants of co-cultures and was demonstrated to have been secreted mainly from BM-MSCs under the influence of D-GalN-injured L02 cells. Constitutive expression of IGF-1R was found in the D-GalN-injured L02 cells and blocking of IGF-1R by a neutralizing antibody significantly inhibited the paracrine pro-proliferative effect of co-cultured BM-MSCs at 24 h, 48 h, and 72 h (t = 2.909, 2.328, and 2.560, respectively; all P less than 0.05).
  
  
  CONCLUSIONS
  BM-MSC-derived IGF-1 plays an important role in the paracrine pro-proliferative effect on D-GalN-injured L02 hepatocytes by engaging with the constitutively expressed IGF-1R on L02 cells.
authors.affiliation: Department of Gastroenterology, Third Military Medical University, Chongqing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Feng
authors.forename: Ji
authors.initials: J
authors.lastname: Xiong
authors.forename: Quan
authors.initials: Q
authors.lastname: Xiong
authors.forename: Xiao-di
authors.initials: XD
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Dong-feng
authors.initials: DF
authors.lastname: Chen
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I