TY - JOUR
T1 - DNA nanoparticles encapsulated in 3D tissue-engineered scaffolds enhance osteogenic differentiation of mesenchymal stem cells
AU - Hosseinkhani, Hossein
AU - Hosseinkhani, Mohsen
AU - Gabrielson, Nathan P.
AU - Pack, Daniel W.
AU - Khademhosseini, Ali
AU - Kobayashi, Hisatoshi
N1 - Funding Information:
We thank the referee, Bo Reipurth, for his critical and careful reading of the manuscript. We thank Spanish DGES for support under grants PB96-0883, PNIE98-1351, and PB96-104.
PY - 2008/4
Y1 - 2008/4
N2 - In this study, we enhanced the expression of a plasmid DNA in mesenchymal stem cells (MSC) by the combination of three-dimensional (3D) tissue-engineered scaffold and nonviral gene carrier. To function as an enhanced delivery of plasmid DNA, acetic anhydride was reacted with polyethylenimine (PEI) to acetylate 80% of the primary and 20% of the secondary amines (PEI-Ac 80). This acetylated PEI has been demonstrated to show enhanced gene-delivery efficiency over unmodified PEI. Collagen sponges reinforced by incorporating of poly(glycolic acid) (PGA) fibers were used as the scaffold material. DNA nanoparticles formed through simple mixing of plasmid DNA encoding bone morphogenetic protein-2 (BMP-2) and PEI-Ac80 solutions were encapsulated within these scaffolds. MSC were seeded into each scaffold and cultured for several weeks. Within these scaffolds, the level of BMP-2 expression by transfected MSC was significantly enhanced compared to MSC transfected by DNA nanoparticles in solution (in 2D tissue culture plates). Homogeneous bone formation was histologically observed throughout the sponges seeded with transfected MSC by using DNA nanoparticles after subcutaneous implantation into the back of rats. The level of alkaline phosphatase activity and osteocalcin content at the implanted sites of sponges seeded with transfected MSC by using DNA nanoparticles were significantly higher when compared with those seeded with other agents.
AB - In this study, we enhanced the expression of a plasmid DNA in mesenchymal stem cells (MSC) by the combination of three-dimensional (3D) tissue-engineered scaffold and nonviral gene carrier. To function as an enhanced delivery of plasmid DNA, acetic anhydride was reacted with polyethylenimine (PEI) to acetylate 80% of the primary and 20% of the secondary amines (PEI-Ac 80). This acetylated PEI has been demonstrated to show enhanced gene-delivery efficiency over unmodified PEI. Collagen sponges reinforced by incorporating of poly(glycolic acid) (PGA) fibers were used as the scaffold material. DNA nanoparticles formed through simple mixing of plasmid DNA encoding bone morphogenetic protein-2 (BMP-2) and PEI-Ac80 solutions were encapsulated within these scaffolds. MSC were seeded into each scaffold and cultured for several weeks. Within these scaffolds, the level of BMP-2 expression by transfected MSC was significantly enhanced compared to MSC transfected by DNA nanoparticles in solution (in 2D tissue culture plates). Homogeneous bone formation was histologically observed throughout the sponges seeded with transfected MSC by using DNA nanoparticles after subcutaneous implantation into the back of rats. The level of alkaline phosphatase activity and osteocalcin content at the implanted sites of sponges seeded with transfected MSC by using DNA nanoparticles were significantly higher when compared with those seeded with other agents.
KW - DNA nanoparticles
KW - Enhanced gene expression
KW - Osteogenic differentiation
KW - Plasmid DNA
KW - Scaffold
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U2 - 10.1002/jbm.a.31327
DO - 10.1002/jbm.a.31327
M3 - Article
C2 - 17688252
AN - SCOPUS:40449108577
SN - 1549-3296
VL - 85
SP - 47
EP - 60
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
IS - 1
ER -