title: Human mesenchymal stromal cells (MSCs) reduce neointimal hyperplasia in a mouse model of flow-restriction by transient suppression of anti-inflammatory cytokines.
abstract: OBJECTIVE
  Mesenchymal stromal cells from human bone marrow (hMSCs) were observed to produce therapeutic benefits in some models for cardiac and vascular injuries but their mode of action was not defined. We tested the effects of hMSCs in models for restricted vascular flow.
  
  
  METHODS
  We made model for restricted vascular flow produced by permanent ligation of a carotid artery and injected hMSCs to clarify the effects of hMSCs to vascular lesions.
  
  
  RESULTS
  Seven, 14, and 28 days after infusion of hMSCs into the cardiac left ventricle of the mice, there was a significant reduction in neointimal hyperplasia (p<0.05). Seven days after administration of the hMSCs, macrophages infiltration into the ligated artery and serum levels of monocyte chemoattractive protein-1 (MCP-1/CCL-2) (p<0.05) were reduced. However, no hMSCs were detected in the lesions by sensitive PCR assays. We then observed that the serum level of MCP-1 was a potential biomarker for the therapeutic effects of hMSCs in a mouse model for high-fat-diet.
  
  
  CONCLUSIONS
  These results indicated the administration of hMSCs decreased the initial and excess inflammatory responses to carotid artery ligation. The decrease in inflammatory response apparently decreased the subsequent neointimal hyperplasia.
authors.affiliation: Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. mashoji@hotmail.com
authors.forename: Makoto
authors.initials: M
authors.lastname: Shoji
authors.forename: Adam
authors.initials: A
authors.lastname: Oskowitz
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Malone
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Prockop
authors.forename: Radhika
authors.initials: R
authors.lastname: Pochampally
mesh_terms: D020087:Alu Elements / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D015153:Blotting, Western; D002339:Carotid Arteries / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D058426:Neointima / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology*; D057772:Vascular System Injuries / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012333:RNA, Messenger