PMID- 19935005
OWN - NLM
STAT- MEDLINE
DCOM- 20100305
LR  - 20131121
IS  - 1524-4040 (Electronic)
IS  - 0148-396X (Linking)
VI  - 65
IP  - 6 Suppl
DP  - 2009 Dec
TI  - Large-scale bicortical skull bone regeneration using ex vivo 
      replication-defective adenoviral-mediated bone morphogenetic protein-2 
      gene-transferred bone marrow stromal cells and composite biomaterials.
PG  - 75-81; discussion 81-3
LID - 10.1227/01.NEU.0000345947.33730.91 [doi]
AB  - OBJECTIVE: Bone marrow stromal cells (BMSCs) have great potential in bone repair. 
      We developed an animal model to test the hypothesis that ex vivo gene transfer of 
      human bone morphogenetic protein (BMP)-2 to BMSCs via a replication-defective 
      (E1A-deleted) adenovirus vector (AdV) with appropriate biopolymers would enhance 
      autologous bone formation during repair of a large-scale skull defect. METHODS: 
      Eighteen miniature swine were treated with AdV BMP-2-transduced BMSCs in 
      biopolymer (group 1), BMSCs in biopolymer (group 2), or biopolymer alone (group 
      3). After 6 months, the swine were killed, and the skull repair was examined by 
      gross pictures, histology, 3-dimensional computed tomography, and biomechanical 
      study. RESULTS: Group 1 showed complete solid bone formation after 6 months, and 
      hematoxylin and eosin staining demonstrated the presence of mature, woven, 
      well-mineralized bone. Computed tomography showed wholesome repair of the skull 
      defect. Statistical analysis demonstrated a significant difference in bone 
      thickness between groups 1 and 2. Biomechanical testing showed a statistically 
      significant difference in the stiffness of new bone formed in group 1 compared 
      with group 2. CONCLUSION: The Ad5 E1A-deleted AdV may be the optimal starting 
      vector in ex vivo gene therapy for benign skeletal diseases. Additionally, the 
      use of the gelatin/tricalcium phosphate ceramic/glutaraldehyde biopolymer with 
      AdV BMP-2 gene transfer strongly enhances the bony healing of critical-size 
      bicortical craniofacial defects. This method can be used by modifying the 
      delivery of constructs to malunion treatment, in regional osteoporosis therapy, 
      and spinal fusion.
FAU - Chang, Sophia Chia-Ning
AU  - Chang SC
AD  - Department of Plastic Surgery, China Medical University Hospital, and School of 
      Medicine, China Medical University, Taichung, Taiwan, Republic of China.
FAU - Lin, Tsung-Min
AU  - Lin TM
FAU - Chung, Hui-Ying
AU  - Chung HY
FAU - Chen, Philip Kuo-Ting
AU  - Chen PK
FAU - Lin, Feng-Huei
AU  - Lin FH
FAU - Lou, Jeuren
AU  - Lou J
FAU - Jeng, Long-Bin
AU  - Jeng LB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurosurgery
JT  - Neurosurgery
JID - 7802914
RN  - 0 (BMP2 protein, human)
RN  - 0 (Biocompatible Materials)
RN  - 0 (Biopolymers)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Substitutes)
RN  - 0 (Calcium Phosphates)
RN  - K4C08XP666 (tricalcium phosphate)
RN  - T3C89M417N (Glutaral)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Biocompatible Materials/chemistry/therapeutic use
MH  - Biopolymers/chemistry/therapeutic use
MH  - Bone Marrow Transplantation/*methods
MH  - Bone Morphogenetic Protein 2/*genetics
MH  - Bone Regeneration/*genetics
MH  - *Bone Substitutes
MH  - Calcium Phosphates/chemistry/therapeutic use
MH  - Cells, Cultured
MH  - Craniotomy/adverse effects/methods
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors/genetics
MH  - Glutaral/chemistry/therapeutic use
MH  - Models, Animal
MH  - Skull/cytology/physiology/surgery
MH  - Stromal Cells/cytology/*metabolism/*transplantation
MH  - Sus scrofa
MH  - Treatment Outcome
MH  - Virus Replication/genetics
MH  - Wound Healing/physiology
EDAT- 2009/12/16 06:00
MHDA- 2010/03/06 06:00
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/12/16 06:00 [pubmed]
PHST- 2010/03/06 06:00 [medline]
AID - 00006123-200912001-00008 [pii]
AID - 10.1227/01.NEU.0000345947.33730.91 [doi]
PST - ppublish
SO  - Neurosurgery. 2009 Dec;65(6 Suppl):75-81; discussion 81-3. doi: 
      10.1227/01.NEU.0000345947.33730.91.