title: Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice.
abstract: OBJECTIVE
  Recent clinical trials use cell therapy with bone marrow (BM) cells or endothelial progenitor cells (EPCs) for ischemic syndromes. We explored the effect of BM cell- or spleen cell-derived EPC transfer on plaque size and stability markers in the apolipoprotein E knockout (apoE KO) mouse model.
  
  
  RESULTS
  ApoE KO mice aged 10 weeks served as recipients. Labeled BM cells and spleen cell-derived EPCs from age-matched apoE KO mice were injected intravenously to 2 groups of recipient mice each. Additional mice served as controls receiving saline. Both protocols were repeated 3 times at 2 weekly intervals. On killing, plaque size and character were studied, lipid profile analyzed, and serum and aortic cytokines assayed. Spleen cell-derived cells contained a significantly larger number of endothelial cell precursors. Labeled EPCs and BM cells were found abundantly in the spleens, yet also in the lesions of the recipient mice. Aortic sinus lesion size was significantly increased in mice receiving BM cells (n=10) in the EPC-treated group (n=10) compared with controls (n=10; a 54% and a 34% increase in aortic sinus plaque area, respectively). Mice receiving EPCs exhibited plaques with larger lipid cores and thinner fibrous caps and a higher number of infiltrating CD3 cells. RT-PCR analysis of aortas revealed reduced expression of mRNA for interleukin-10 (IL-10) in both cell transfer groups. Higher serum concentrations of IL-6 and monocyte chemoattractant protein-1 were found in sera from BM recipients, whereas lower IL-10 levels were found in mice transfused with spleen-derived EPCs.
  
  
  CONCLUSIONS
  Transfer of BM cells and EPCs may result in an increase in atherosclerotic lesion size, whereas EPC transfer could also potentially influence plaque stability.
authors.affiliation: Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel. jacobg@post.tau.ac.il
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: Arnon
authors.initials: A
authors.lastname: Afek
authors.forename: Anastasia
authors.initials: A
authors.lastname: Abashidze
authors.forename: Haim
authors.initials: H
authors.lastname: Shmilovich
authors.forename: Varda
authors.initials: V
authors.lastname: Deutsch
authors.forename: Juri
authors.initials: J
authors.lastname: Kopolovich
authors.forename: Hylton
authors.initials: H
authors.lastname: Miller
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D015415:Biomarkers; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000276:immunology; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D012850:Sinus of Valsalva / Q000473:pathology / Q000503:physiopathology; D013154:Spleen / Q000166:cytology; D033581:Stem Cell Transplantation
chemical_list: D000906:Antibodies; D001057:Apolipoproteins E; D015415:Biomarkers; D016207:Cytokines; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein