| Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres. | |
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MedLine Citation:
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PMID: 22529991 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yohei Mima; Shinya Fukumoto; Hidenori Koyama; Masahiro Okada; Shinji Tanaka; Tetsuo Shoji; Masanori Emoto; Tsutomu Furuzono; Yoshiki Nishizawa; Masaaki Inaba |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-04-18 |
Journal Detail:
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Title: PloS one Volume: 7 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2012 |
Date Detail:
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Created Date: 2012-04-24 Completed Date: 2012-11-19 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e35199 Citation Subset: IM |
Affiliation:
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Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inducing Agents
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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:
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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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