title: Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells.
abstract: BACKGROUND
  Induction of angiogenic mechanisms to promote development of collateral vessels is considered promising for the treatment of peripheral arterial diseases. Collateral vessels generally develop from preexisting arteriolar connections, bypassing the diseased artery. We speculated that induction of angiogenic mechanisms should be directed to such arteriolar connections to achieve efficient collateral development. The aim of this study was to verify this hypothesis using autologous transplantation of bone marrow mononuclear cells in the rabbit model of chronic limb ischemia.
  
  
  RESULTS
  The left femoral artery was excised to induce limb ischemia in male rabbits. In this model, arteriolar connections in the left coccygeofemoral muscle tend to develop into collateral vessels, although this transformation is insufficient to alleviate the limb ischemia. In contrast, arteriolar connections in the closely located adductor muscle do not readily develop into collateral vessels. At 21 days after ischemia initiation, a sufficient number of automononuclear cells were selectively injected in the left coccygeofemoral muscle (coccygeo group) or left adductor muscle (adductor group). Evaluation of calf blood pressure ratios, blood flow in the left internal iliac artery, and angiographic scores at day 28 after injection revealed that collateral development and improvement of limb ischemia were significantly more efficient in the coccygeo group than in the adductor group. Morphometric analysis of the coccygeofemoral muscle at day 14 showed similar results.
  
  
  CONCLUSIONS
  Specific delivery of mononuclear cells to the coccygeofemoral but not the adductor muscle effectively improves collateral circulation in the rabbit model of limb ischemia and suggests that adequate site selection can facilitate therapeutic angiogenesis.
authors.affiliation: Department of Vascular Surgery, Graduate School of Medicine, University of Tokyo, Japan (M.N., H.K., A.N., K.S., T.W.).
authors.forename: Masaru
authors.initials: M
authors.lastname: Nemoto
authors.affiliation: Department of Vascular Surgery, Graduate School of Medicine, University of Tokyo, Japan (M.N., H.K., A.N., K.S., T.W.) Translational Research Center, The University of Tokyo Hospital, Tokyo, Japan (H.K.) Department of Vascular Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan (H.K.).
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Department of Vascular Surgery, Graduate School of Medicine, University of Tokyo, Japan (M.N., H.K., A.N., K.S., T.W.).
authors.forename: Ayako
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Vascular Surgery, Graduate School of Medicine, University of Tokyo, Japan (M.N., H.K., A.N., K.S., T.W.).
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Shigematsu
authors.affiliation: Vascular Center, Sanno Hospital and Sanno Medical Center, Tokyo, Japan (T.M.).
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Department of Vascular Surgery, Graduate School of Medicine, University of Tokyo, Japan (M.N., H.K., A.N., K.S., T.W.).
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D003097:Collateral Circulation; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000503:physiopathology / Q000601:surgery; D006614:Hindlimb; D007083:Iliac Artery / Q000503:physiopathology; D007511:Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011817:Rabbits; D011859:Radiography; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: arteriogenesis; collateral circulation; ischemia