Abstract
This study was performed to determine if a combination of previously undifferentiated bone marrow-derived mesenchymal stem cells (BMMSCs) and exogenous bone morphogenetic protein-2 (BMP-2) delivered via heparin-conjugated PLGA nanoparticles (HCPNs) would extensively regenerate bone in vivo. In vitro testing found that the HCPNs were able to release BMP-2 over a 2-week period. Human BMMSCs cultured in medium containing BMP-2-loaded HCPNs for 2 weeks differentiated toward osteogenic cells expressing alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN) mRNA, while cells without BMP-2 expressed only ALP. In vivo testing found that undifferentiated BMMSCs with BMP-2-loaded HCPNs induce far more extensive bone formation than either implantation of BMP-2-loaded HCPNs or osteogenically differentiated BMMSCs. This study demonstrates the feasibility of extensive in vivo bone regeneration by transplantation of undifferentiated BMMSCs and BMP-2 delivery via HCPNs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biocompatible Materials / administration & dosage
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Biocompatible Materials / chemistry
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Bone Morphogenetic Protein 2 / administration & dosage
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Bone Morphogenetic Protein 2 / pharmacokinetics
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Bone Morphogenetic Protein 2 / pharmacology*
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Cell Differentiation / drug effects
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Cells, Cultured
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Female
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Fibrinolytic Agents / administration & dosage
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Fibrinolytic Agents / chemistry
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Fibrinolytic Agents / pharmacology*
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Heparin / administration & dosage
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Heparin / chemistry
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Heparin / pharmacology*
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Humans
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Lactic Acid / administration & dosage
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Lactic Acid / chemistry*
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Male
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Mesenchymal Stem Cell Transplantation
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Mice
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Microscopy, Electron, Scanning
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Middle Aged
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry*
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Nanoparticles / ultrastructure
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Osteogenesis / drug effects*
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Polyglycolic Acid / administration & dosage
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Polyglycolic Acid / chemistry*
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Polylactic Acid-Polyglycolic Acid Copolymer
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Time Factors
Substances
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Biocompatible Materials
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Bone Morphogenetic Protein 2
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Fibrinolytic Agents
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid
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Heparin