title: Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres.
abstract: BACKGROUND
  Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis in patients with severe ischemic diseases; however, their success remains limited. Maintaining transplanted cells in place are expected to augment the cell-based therapeutic angiogenesis. We have reported that nano-hydroxyapatite (HAp) coating on medical devices shows marked cell adhesiveness. Using this nanotechnology, HAp-coated poly(l-lactic acid) (PLLA) microspheres, named nano-scaffold (NS), were generated as a non-biological, biodegradable and injectable cell scaffold. We investigate the effectiveness of NS on cell-based therapeutic angiogenesis.
  
  
  RESULTS
  Bone marrow mononuclear cells (BMNC) and NS or control PLLA microspheres (LA) were intramuscularly co-implanted into mice ischemic hindlimbs. When BMNC derived from enhanced green fluorescent protein (EGFP)-transgenic mice were injected into ischemic muscle, the muscle GFP level in NS+BMNC group was approximate fivefold higher than that in BMNC or LA+BMNC groups seven days after operation. Kaplan-Meier analysis demonstrated that NS+BMNC markedly prevented hindlimb necrosis (P<0.05 vs. BMNC or LA+BMNC). NS+BMNC revealed much higher induction of angiogenesis in ischemic tissues and collateral blood flow confirmed by three-dimensional computed tomography angiography than those of BMNC or LA+BMNC groups. NS-enhanced therapeutic angiogenesis and arteriogenesis showed good correlations with increased intramuscular levels of vascular endothelial growth factor and fibroblast growth factor-2. NS co-implantation also prevented apoptotic cell death of transplanted cells, resulting in prolonged cell retention.
  
  
  CONCLUSIONS
  A novel and feasible injectable cell scaffold potentiates cell-based therapeutic angiogenesis, which could be extremely useful for the treatment of severe ischemic disorders.
authors.affiliation: Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mima
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shoji
authors.forename: Masanori
authors.initials: M
authors.lastname: Emoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Furuzono
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000379:methods*; D003097:Collateral Circulation; D004195:Disease Models, Animal; D017886:Durapatite; D005121:Extremities / Q000098:blood supply; D007511:Ischemia / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D053761:Nanocomposites / Q000008:administration & dosage / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D054457:Tissue Scaffolds
chemical_list: D043925:Angiogenesis Inducing Agents; D001672:Biocompatible Materials; D017886:Durapatite