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Micro-CT를 이용한 BMP-2 유전자가 형질 도입된 지방 줄기세포의 흰쥐 두개골 결손부의 골형성 평가

Evaluation of bone regeneration of rat cranial defect using BMP-2 transduced human adipose-derived stem cells by micro-CT

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Objective: Adipose-derived stem cells (ADSC) have been reported to differentiate to osteogenic cell under proper stimuli and condition. The objective of the present study was to assess the bone regeneration capacity of genetically modified ADSC expressing BMP-2 by transduction with recombinant adenovirus (Ad/BMP-2) in uniform microporous bead poly-lactic-co-glycolic acid (PLGA) scaffold by microstructural analysis with 3D micro-CT. Material and methods: A 5-mm critical-sized full-thickness bone defects were created on the parietal bones of 24 rats (two defects a rat) using a trephine bur. The defects were either left empty or restored with a PLGA scaffold alone, or transplanted with ADSC in osteogenic media or transplanted with Ad/BMP-2 transduced ADSC. Six calvarial defects were analyzed for each group with micro-CT imaging at 4 and 8 weeks after transplantation, respectively. Results: Adenoviral transduction of BMP-2 gene was successfully accomplished on ADSC. And improved new bone regeneration was observed in Ad/BMP-2 transduced ADSC loaded defect as compared to control group that showed minimal healing. Especially, statistical significance were found in variables like bone volume, percent bone volume, bone surface new bone formation in Ad/BMP-2 transduced ADSCs at both time points. Conclusion: This result demonstrates that the genetically transferred BMP-2 enhances the ossification ability of ADSCs, and uniform microporous bead PLGA scaffold confirmed its suitability for bone tissue engineering. Under limitation of this study, genetically modification of ADSC with osteogenic gene could be adopted to clinical trial.

Abstract

Objective: Adipose-derived stem cells (ADSC) have been reported to differentiate to osteogenic cell under proper stimuli and condition. The objective of the present study was to assess the bone regeneration capacity of genetically modified ADSC expressing BMP-2 by transduction with recombinant adenovirus (Ad/BMP-2) in uniform microporous bead poly-lactic-co-glycolic acid (PLGA) scaffold by microstructural analysis with 3D micro-CT. Material and methods: A 5-mm critical-sized full-thickness bone defects were created on the parietal bones of 24 rats (two defects a rat) using a trephine bur. The defects were either left empty or restored with a PLGA scaffold alone, or transplanted with ADSC in osteogenic media or transplanted with Ad/BMP-2 transduced ADSC. Six calvarial defects were analyzed for each group with micro-CT imaging at 4 and 8 weeks after transplantation, respectively. Results: Adenoviral transduction of BMP-2 gene was successfully accomplished on ADSC. And improved new bone regeneration was observed in Ad/BMP-2 transduced ADSC loaded defect as compared to control group that showed minimal healing. Especially, statistical significance were found in variables like bone volume, percent bone volume, bone surface new bone formation in Ad/BMP-2 transduced ADSCs at both time points. Conclusion: This result demonstrates that the genetically transferred BMP-2 enhances the ossification ability of ADSCs, and uniform microporous bead PLGA scaffold confirmed its suitability for bone tissue engineering. Under limitation of this study, genetically modification of ADSC with osteogenic gene could be adopted to clinical trial.

참고문헌 (49)

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