title: Mesenchymal stem cells can participate in ischemic neovascularization.
abstract: BACKGROUND
  Cells from the bone marrow contribute to ischemic neovascularization, but the identity of these cells remains unclear. The authors identify mesenchymal stem cells as a bone marrow-derived progenitor population that is able to engraft into peripheral tissue in response to ischemia.
  
  
  METHODS
  A murine model of skin ischemia was used. Bone marrow, blood, and skin were harvested at different time points and subjected to flow cytometric analysis for mesenchymal and hematopoietic markers (n = 3 to 7 per time point). Using a parabiotic model pairing donor green fluorescent protein (GFP)-positive with recipient wild-type mice, progenitor cell engraftment was examined in ischemic tissue by fluorescence microscopy, and engrafted cells were analyzed by flow cytometry for endothelial and mesenchymal markers. In vitro, the ability of both bone marrow- and adipose-derived mesenchymal stem cells to adopt endothelial characteristics was examined by analyzing (1) the ability of mesenchymal stem cells to take up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and (2) phenotypic changes of mesenchymal stem cells co-cultured with GFP-labeled endothelial cells or under hypoxic/vascular endothelial growth factor stimulation.
  
  
  RESULTS
  In vivo, the bone marrow mesenchymal stem cell population decreased significantly immediately after surgery, with subsequent engraftment of these cells in ischemic tissue. Engrafted cells lacked the panhematopoietic antigen CD45, consistent with a mesenchymal origin. In vitro, bone marrow- and adipose-derived mesenchymal stem cells took up DiI-acetylated low-density lipoprotein and Alexa Fluor lectin, and expressed endothelial markers under hypoxic conditions.
  
  
  CONCLUSIONS
  The authors' data suggest that mesenchymal precursor cells can give rise to endothelial progenitors. Consequently, cell-based therapies augmenting the mesenchymal stem cell population could represent powerful alternatives to current therapies for ischemic vascular disease.
authors.affiliation: Stanford, Calif. From the Department of Surgery, Division of Plastic Surgery, Stanford University School of Medicine.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hamou
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Callaghan
authors.forename: Hariharan
authors.initials: H
authors.lastname: Thangarajah
authors.forename: Edwin
authors.initials: E
authors.lastname: Chang
authors.forename: Eric I
authors.initials: EI
authors.lastname: Chang
authors.forename: Raymon H
authors.initials: RH
authors.lastname: Grogan
authors.forename: Josemaria
authors.initials: J
authors.lastname: Paterno
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Vial
authors.forename: Leila
authors.initials: L
authors.lastname: Jazayeri
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000502:physiology; D007511:Ischemia / Q000628:therapy*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012867:Skin / Q000098:blood supply*