Abstract
Aim:
Bone morphogenetic protein 4 (BMP4) is one of the main local contributing factors in callus formation in the early phase of fracture healing. Adipose-derived stromal cells (ADSC) are multipotent cells. The present study was conducted to investigate the osteogenic potential of ADSC when exposed to adenovirus containing BMP4 cDNA (Ad-BMP4).
Methods:
ADSC were harvested from Sprague-Dawley rats. After exposure to Ad-BMP4, ADSC were assessed by alkaline phosphatase activity (ALP) assay, RT-PCR and von Kossa staining. BMP4 expression was assessed by RT-PCR, immunofluorescence and Western blot analysis. ADSC transduced with Ad-BMP4 were directly injected into the hind limb muscles of athymic mice. ADSC Ad-EGFP(enhanced green fluorescence protein) served as controls. All animals were examined by X-ray film and histological analysis.
Results:
The expression of BMP4 was confirmed at both mRNA and protein levels. The expression of the osteoblastic gene, ALP activity and von Kossa staining confirmed that ADSC transduced with Ad-BMP4 underwent rapid and marked osteoblast differentiation, whereas ADSC transduced with Ad-EGFP and cells left alone displayed no osteogenic differentiation. X-ray and histological examination confirmed new bone formation in athymic mice transplanted with ADSC transduced with Ad-BMP4.
Conclusion:
Our data demonstrated successful osteogenic differentiation of ADSC transduced with Ad-BMP4 in vitro and in vivo. ADSC maybe an ideal source of mesenchyme lineage stem cells for gene therapy and tissue engineering.
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Project supported by the program of gene therapy on sports injury sponsored by the State Sports General Administration of China.
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Lin, L., Fu, X., Zhang, X. et al. Rat adipose-derived stromal cells expressing BMP4 induce ectopic bone formation in vitro and in vivo. Acta Pharmacol Sin 27, 1608–1615 (2006). https://doi.org/10.1111/j.1745-7254.2006.00449.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00449.x
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