title: Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice.
abstract: OBJECTIVE
  Vein graft endothelial damage is a key step in the development of neointimal hyperplasia, leading to vein graft failure. We sought to determine whether exogenous endothelial progenitor cells could promote vein graft re-endothelialization, and thereby ameliorate neointimal hyperplasia.
  
  
  RESULTS
  Carotid artery interposition grafting was performed with syngeneic inferior vena cavae in mice with severe combined immunodeficiency (SCID). Lineage-negative human umbilical cord blood (hUCB) cells (or medium alone) were injected into vein-grafted mice intra-operatively and 2 weeks post-operatively. In vein grafts from hUCB cell-injected mice, we found human HLA-expressing endothelial cells, as well as increased levels of VEGF and FGF-2. Furthermore, hUCB cells secreted VEGF and FGF-2 in vitro. The markedly enhanced endothelial regeneration, likely resulting from both direct engraftment and paracrine actions of hUCB cells, inhibited inflammatory response, diminished intimal cell proliferation, and reduced neointimal hyperplasia in the vein grafts.
  
  
  CONCLUSIONS
  hUCB cells may accelerate vein graft re-endothelialization via both direct differentiation into endothelial cells and release of paracrine factors to enhance endothelial regeneration and reduce inflammation. These data highlight a potential therapeutic role for cellular therapy in vessel injury.
authors.affiliation: Miller School of Medicine, University of Miami, FL 33101, USA.
authors.forename: Shoukang
authors.initials: S
authors.lastname: Zhu
authors.forename: Anuj
authors.initials: A
authors.lastname: Malhotra
authors.forename: Lisheng
authors.initials: L
authors.lastname: Zhang
authors.forename: Shanming
authors.initials: S
authors.lastname: Deng
authors.forename: Taifang
authors.initials: T
authors.lastname: Zhang
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Freedman
authors.forename: Robert
authors.initials: R
authors.lastname: Storms
authors.forename: Karsten
authors.initials: K
authors.lastname: Peppel
authors.forename: Pascal J
authors.initials: PJ
authors.lastname: Goldschmidt-Clermont
authors.forename: Chunming
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D049109:Cell Proliferation; D036101:Cord Blood Stem Cell Transplantation; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006085:Graft Survival; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D019899:Paracrine Communication; D012038:Regeneration; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014682:Vena Cava, Inferior / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
chemical_list: D006680:HLA Antigens; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2
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