title: MSC(TRAIL)-mediated HepG2 cell death in direct and indirect co-cultures.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy since the discovery of their tumor tropism. This study was performed to investigate the effects of TNF-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on hepatocellular carcinoma (HCC) cells (HepG2) under different culture conditions.
  
  
  METHODS
  MSCs engineered with non-secreting TRAIL (MSC(TRAIL-GFP)) (GFP, green fluorescence protein) and secreting TRAIL (MSC(stTRAIL)) were used for the direct co-cultures, and conditioned media (CM) from corresponding cultures were applied to HepG2 as indirect co-cultures. Immunoblotting, ELISA and FACS analysis were used to detect the expression of TRAIL and TRAIL receptors. Cell death was assessed using live/dead assay.
  
  
  RESULTS
  Death receptor (DR) 5 was identified on the HepG2 cells. The expression of TRAIL was confirmed in the cell lysates (MSC(TRAIL-GFP) >MSC(stTRAIL)) and the conditioned media (MSC(stTRAIL) >MSC(TRAIL-GFP)). Higher cell death was observed in high MSC/HepG2 ratio co-cultures. HepG2 cell death was proportionally related to CM from MSC(TRAIL-GFP) and MSC(stTRAIL).
  
  
  CONCLUSIONS
  MSCs exhibit intrinsic inhibition of HepG2 which is potentiated by TRAIL-transfection.
authors: Institute of Transplant Medicine, 303 Hospital of PLA, Nanning, PR China.
authors: Xu-Yong
authors: XY
authors: Sun
authors: Jiang
authors: J
authors: Nong
authors: Ke
authors: K
authors: Qin
authors: Hong
authors: H
authors: Lu
authors: Mani R
authors: MR
authors: Moniri
authors: Long-Jun
authors: LJ
authors: Dai
authors: Garth L
authors: GL
authors: Warnock
mesh_terms: D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D002102:Cadaver; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D017077:Culture Media, Conditioned; D053221:TNF-Related Apoptosis-Inducing Ligand