Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts promotes bone regeneration in rats.
OBJECTIVE
The aim of the present study was to investigate bone regeneration following ex vivo bone morphogenetic protein-2 (BMP-2) gene delivery using human gingival fibroblasts (HGFs) in rat calvarial defects.


METHODS
An 8 mm craniotomy defect was created in Sprague-Dawley rats. The animals were divided into four groups: (1) non-grafted group, the defect was left empty; (2) collagen matrix group, the defect was filled with collagen matrix only; (3) HGF group, the defect was filled with non-transduced HGFs on collagen matrix; (4) BMP-2/HGF group, the defect was filled with BMP-2 gene-transduced HGFs on collagen matrix. Animals were sacrificed at 2 and 4 weeks after surgery, and micro-computed tomographic and histologic observations were performed.


RESULTS
The BMP-2/HGF group showed promoted osseous healing of calvarial defects, as compared with the other groups. At both 2 and 4 weeks, regenerated bone area was significantly greater in the BMP-2/HGF group than the other three groups. Quite a few number of transplanted HGFs were observed within the regenerated bone tissues.


CONCLUSIONS
The results of this study suggest that ex vivo BMP-2 gene delivery induces prominent bone regeneration in vivo and HGFs may be useful as target cells for ex vivo gene therapy.
Shin
Joong-Ho
JH
Department of Periodontology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
Kim
Kyoung-Hwa
KH
Kim
Su-Hwan
SH
Koo
Ki-Tae
KT
Kim
Tae-Il
TI
Seol
Yang-Jo
YJ
Ku
Young
Y
Rhyu
In-Chul
IC
Chung
Chong-Pyoung
CP
Lee
Yong-Moo
YM
D000293:Adolescent; D000818:Animals; D001857:Bone Matrix / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology*; D018786:Bone Substitutes; D002478:Cells, Cultured; D003399:Craniotomy; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005881:Gingiva / Q000166:cytology; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D020007:Implants, Experimental; D008297:Male; D016348:Osseointegration / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes