Combination of beta-TCP and BMP-2 gene-modified bMSCs to heal critical size mandibular defects in rats.
OBJECTIVE
To investigate the effects of mandibular defects repaired by a tissue engineered bone complex with beta-tricalcium phosphate (beta-TCP) and bone morphogenic protein-2 (BMP-2) gene-modified bone marrow stromal cells (bMSCs).


METHODS
bMSCs derived from Fisher 344 rats were cultured and transduced with adenovirus AdBMP-2, AdEGFP gene in vitro. Osteogenic differentiation of bMSCs was determined by alkaline phosphatase staining, von Kossa assay and reverse transcription-polymerase chain reaction. Gene transduced or untransduced bMSCs were seeded on beta-TCP scaffolds to repair mandibular full thickness defects with a diameter of 5 mm. Eight weeks post-operation, X-ray examination, micro-computerized tomography and histological and histomorphological analysis were used to evaluate the bone healing effects.


RESULTS
Alkaline phosphatase staining and mineralized nodules formation were more pronounced in AdBMP-2 group 14 days after gene transduction when compared with that of AdEGFP or untransduced group. The mRNA expression of osteopontin and osteocalcin also significantly increased 9 days after AdBMP-2 gene transduction. Mandibular defects were successfully repaired with AdBMP-2-transduced bMSCs/beta-TCP constructs. The percentage of new bone formation in AdBMP-2 group was significantly higher than that of other control groups.


CONCLUSIONS
Bone morphogenic protein-2 regional gene therapy together with beta-TCP scaffold could be used to promote mandibular repairing and bone regeneration.
Zhao
J
J
Department of Oral and Maxillofacial Surgery, College of Stomatology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, 200011 Shanghai, China.
Hu
J
J
Wang
S
S
Sun
X
X
Xia
L
L
Zhang
X
X
Zhang
Z
Z
Jiang
X
X
D000818:Animals; D016026:Bone Marrow Transplantation; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates; D002478:Cells, Cultured; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D008334:Mandible / Q000601:surgery; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000637:transplantation*; D054457:Tissue Scaffolds; D014161:Transduction, Genetic; D055114:X-Ray Microtomography
D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate; D015675:Osteocalcin; D053495:Osteopontin