title: Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model.
abstract: BACKGROUND
  We evaluated the effect of autologous marrow stromal cells (MSCs) on neovascularization and blood flow in an animal model of chronic limb ischemia.
  
  
  METHODS
  Chronic hind limb ischemia was created by ligating the left common iliac artery of male Lewis rats. Three weeks after ligation, 5.0 million LacZ+MSCs (n = 10) or culture medium (n = 10) were injected into the anteromedial muscle compartment of the left thigh. At 4 and 6 weeks after injection, half the animals (n = 5) from each group underwent femoral artery ultrasonic blood flow measurements of the ischemic and nonischemic limbs to obtain a flow ratio. The animals also underwent angiography and measurements of blood vessel density and arteriolar density. Qualitative histologic assessment of the limb muscles was performed.
  
  
  RESULTS
  LacZ+MSCs were found to differentiate into endothelium (F VIII+), vascular smooth muscle (positive a-smooth muscle actin), skeletal muscle (positive desmin), and adipocytes. Ischemic hind limbs where MSCs were implanted had greater vascular density and arteriolar density than control limbs (p < 0.001). Femoral artery flow index (left femoral artery flow/right femoral artery flow) was 0.89 +/- 0.12 and 0.90 +/- 0.06 for rats injected with MSCs measured at 4- and 6-weeks, respectively, compared with 0.50 +/- 0.15 and 0.50 +/- 0.10 for the control rats (p < 0.001). Angiography demonstrated reconstitution of the left femoral artery in rats that received MSC implantation through pelvic and abdominal wall collateral formation.
  
  
  CONCLUSIONS
  Local MSC implantation induces a neovascular response resulting in a significant increase in blood flow to the ischemic limb. Marrow stromal cells are also capable of spontaneously regenerating the various components of muscular tissues.
authors.affiliation: Division of Cardiothoracic Surgery, Lady Davis Institute for Medical Research, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Al-Khaldi
authors.forename: Hilal
authors.initials: H
authors.lastname: Al-Sabti
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
authors.forename: Kevin
authors.initials: K
authors.lastname: Lachapelle
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D007511:Ischemia / Q000628:therapy*; D007866:Leg / Q000098:blood supply*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D017154:Stromal Cells / Q000637:transplantation; D014182:Transplantation, Autologous