Document Detail


Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres.
MedLine Citation:
PMID:  22529991     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
METHODS AND 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.
CONCLUSION: 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:
Yohei Mima; Shinya Fukumoto; Hidenori Koyama; Masahiro Okada; Shinji Tanaka; Tetsuo Shoji; Masanori Emoto; Tsutomu Furuzono; Yoshiki Nishizawa; Masaaki Inaba
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-18
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-24     Completed Date:  2012-11-19     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e35199     Citation Subset:  IM    
Affiliation:
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inducing Agents / metabolism
Animals
Apoptosis
Biocompatible Materials / administration & dosage
Bone Marrow Transplantation / methods*
Collateral Circulation
Disease Models, Animal
Durapatite
Extremities / blood supply
Ischemia / metabolism,  therapy*
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Microspheres
Nanocomposites / administration & dosage,  ultrastructure
Neovascularization, Physiologic*
Tissue Scaffolds
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Biocompatible Materials; 1306-06-5/Durapatite
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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