title: Mouse mesenchymal stem cells from bone marrow differentiate into smooth muscle cells by induction of plaque-derived smooth muscle cells.
abstract: OBJECTIVE
  The present study aimed to elucidate the mechanism by which bone marrow mesenchymal stem cells (BMSCs) differentiate into smooth muscle cells (SMCs) in atherosclerosis.
  
  
  METHODS
  We isolated mouse BMSCs and incubated them in conditioned medium from plaque-derived SMCs (SMC-CM) and analyzed growth factors from media. BMSCs were treated with different media and harvested at continuous time points for investigating the ability to differentiate toward SMCs. Next, BMSCs of green fluorescence protein (GFP) mice were transplanted into apolipoprotein E(-/-) (apoE(-/-)) mice fed on western type diet for 12 weeks. In vivo efficacy of BMSCs was investigated.
  
  
  RESULTS
  After being cultured using SMC-CM, hepatocyte growth factor (HGF) was abundantly secreted into the medium by BMSCs with time. BMSCs had increased expression of HGF receptor c-met and SMC-specific markers while they also displayed SMC characteristic 'hill and valley-like' appearance with an SMC ultra-structure including actin filaments and dense bodies. In vivo-grafted BMSCs aggravated atherosclerotic lesions and inflammation but ameliorated fibrosis in aorta while they displayed higher expression levels of c-met and early SMC-specific markers but not late-stage markers in aorta. They also demonstrated greater secretion of HGF in the aorta of apoE(-/-) mice. Furthermore, when BMSCs were treated with HGF blocking antibody, they lost the ability to differentiate to SMCs.
  
  
  CONCLUSIONS
  HGF from local SMCs plays an important role for the differentiation of homing BMSCs.
authors.affiliation: Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Mincai
authors.initials: M
authors.lastname: Li
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Qu
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Ruan
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000503:physiopathology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D017077:Culture Media, Conditioned; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D032389:Myocytes, Smooth Muscle / Q000648:ultrastructure*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor