Cranial repair using BMP-2 gene engineered bone marrow stromal cells.
BACKGROUND
Bone grafts, allografts, and biocompatible artificial bone substitutes all have their shortcomings when used for the repair of cranial bone defects. Tissue engineered bone shows promise as an alternative for the repair of these defects.


METHODS
Rabbit bone marrow mesenchymal stromal cells (MSCs) were separated from iliac crest aspirates and expanded in a monolayer culture 1 month before implantation. These MSCs were then infected with replication-defective adenovirus-human BMP-2 genes 1 week before implantation. Bilateral critical-size cranial defects were created in the animal with removal of osteoinductive periosteum and dura. MSCs were mixed with alginate UP (ultrapure) to form MSC/polymer construct. MSCs used for the control site were infected with adenovirus beta-galactosidase (beta-gal). After 1 week, 6 weeks, and 3 months, five rabbits from each experimental group were sacrificed and the cranial defect site was examined by histology study.


RESULTS
Near-complete repair of the large size cranial defects using the tissue engineered MSC/alginate construct was observed. The H&E stain and von Kossa's staining should better regenerate bone at the experiment site. A statistically significant difference in bone formation was noted by 3D CT imaging at 3 months post-BMP-2 treatment of the cranial defects (0.79 +/- 0.06 versus 0.47 +/- 0.05 cm(2), P < 0.001) but not at 6 weeks (0.36 +/- 0.04 versus 0.33 +/- 0.03 cm(2), P = 0.347).


CONCLUSIONS
Near-complete repair of large cranial defects can be achieved using tissue engineered bone. The use of newly developed polymers as well as the integration of the stem cell concept with gene medicine is necessary to attain this goal.
Chang
Sophia Chia-Ning
SC
Tissue Engineering Center, Department of Plastic Surgery, Chang-Gung Memorial Hospital, Chang Gung Institute of Technology, Taipei, Taiwan. schang@adm.cgmh.org.tw
Chuang
Huoli
H
Chen
Yu-Ray
YR
Yang
Lin-Cheng
LC
Chen
Jan-Kan
JK
Mardini
Samir
S
Chung
Hui-Ying
HY
Lu
Yi-Lung
YL
Ma
Wei-Chun
WC
Lou
Jueren
J
Mardinis
Samir
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001847:Bone Diseases / Q000601:surgery*; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D021621:Imaging, Three-Dimensional; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D017154:Stromal Cells / Q000378:metabolism*; D023822:Tissue Engineering; D014057:Tomography, X-Ray Computed / Q000379:methods; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2