Enhancement of ectopic bone formation by bone morphogenetic protein-2 delivery using heparin-conjugated PLGA nanoparticles with transplantation of bone marrow-derived mesenchymal stem cells.
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.
Kim
Sung Eun
SE
Department of Oral Biology and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, South Korea.
Jeon
Oju
O
Lee
Jung Bok
JB
Bae
Min Soo
MS
Chun
Heoung-Jae
HJ
Moon
Seong-Hwan
SH
Kwon
Il Keun
IK
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013997:Time Factors
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D005343:Fibrinolytic Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006493:Heparin