title: Lack of thrombospondin-2 reduces fibrosis and increases vascularity around cardiac cell grafts.
abstract: BACKGROUND
  Fibrosis around cardiac cell injections represents an obstacle to graft integration in cell-based cardiac repair. Thrombospondin-2 (TSP-2) is a pro-fibrotic, anti-angiogenic matricellular protein and an attractive target for therapeutic knockdown to improve cardiac graft integration and survival.
  
  
  METHODS
  We used a TSP-2 knockout (KO) mouse in conjunction with a fetal murine cardiomyocyte grafting model to evaluate the effects of a lack of TSP-2 on fibrosis, vascular density, and graft size in the heart.
  
  
  RESULTS
  Two weeks after grafting in the uninjured heart, fibrosis area was reduced 4.5-fold in TSP-2 KO mice, and the thickness of the peri-graft scar capsule was reduced sevenfold compared to wild-type (WT). Endothelial cell density in the peri-graft region increased 2.5-fold in the absence of TSP-2, and cardiomyocyte graft size increased by 46% in TSP-2 KO hearts.
  
  
  CONCLUSIONS
  TSP-2 is a key regulator of fibrosis and angiogenesis following cell grafting in the heart, and its absence promotes better graft integration, vascularization, and survival.
  
  
  CONCLUSIONS
  Fibrosis around cardiac cell injections impairs graft integration in cell-based cardiac repair. TSP-2 is a pro-fibrotic, anti-angiogenic matricellular protein. Using a TSP-2-knockout mouse model and cardiac cell transplantation, we found significantly reduced fibrosis and increased endothelial cell density in the peri-graft region. Thus, TSP-2 is an attractive target for therapeutic knockdown to improve cardiac graft integration and survival.
authors.affiliation: Department of Pathology, Center for Cardiovascular Biology and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Robey
authors.forename: John L
authors.initials: JL
authors.lastname: Mignone
authors.forename: Veronica
authors.initials: V
authors.lastname: Muskheli
authors.forename: Paul
authors.initials: P
authors.lastname: Bornstein
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000378:metabolism; D019699:Thrombospondins / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D000099262:Thrombospondin 2
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D012333:RNA, Messenger; D019699:Thrombospondins; D000099262:Thrombospondin 2