title: Uremia induces functional incompetence of bone marrow-derived stromal cells.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is associated with increased risk for cardiovascular diseases (CVD). We hypothesized that inadequate angiogenic response in uremic patients could result from dysfunction of bone marrow-derived stromal cells [mesenchymal stem cells (MSCs)].
  
  
  METHODS
  We investigated whether MSCs are functionally competent in uremia induced by partial kidney ablation in C57Bl/6J mice.
  
  
  RESULTS
  Uremic MSCs showed decreased expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)1 and stromal cell-derived factor (SDF)-1α, increased cellular senescence, decreased proliferation, defects in migration in response to VEGF and SDF-1α and in vitro tube formation. Interestingly, the expression of fibroblast-specific protein-1 was higher in uremic MSCs. Uremia decreased hypoxia-inducible factor-1α, VEGF and VEGFR1 expression under hypoxia and Akt phosphorylation in both basal and VEGF-stimulated states. A diminished mitogenic effect on endothelial proliferation was observed in conditioned media from uremic MSCs. In addition, intravital microscopic analysis showed decreased angiogenesis in uremic MSCs.
  
  
  CONCLUSIONS
  These results clearly demonstrate the functional incompetence in MSCs under uremic conditions and may significantly contribute to the disproportionately high risk for CVD in patients with CKD.
authors.affiliation: Department of Internal Medicine, Soon Chun Hyang University, Seoul, Korea. nohneph@schmc.ac.kr
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Noh
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Yu
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Jeon
authors.forename: Soon Hyo
authors.initials: SH
authors.lastname: Kwon
authors.forename: So Young
authors.initials: SY
authors.lastname: Jin
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Jiryeon
authors.initials: J
authors.lastname: Jang
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Fuad
authors.initials: F
authors.lastname: Ziyadeh
authors.forename: Dong Cheol
authors.initials: DC
authors.lastname: Han
authors.forename: Hi Bahl
authors.initials: HB
authors.lastname: Lee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000209:etiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014511:Uremia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D051057:Proto-Oncogene Proteins c-akt