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间充质干细胞介导的骨形态发生蛋白-2在关节骨折模型中的基因递送

Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in an articular fracture model.

作者信息

Zachos Terri, Diggs Alisha, Weisbrode Steven, Bartlett Jeffrey, Bertone Alicia

机构信息

Comparative Orthopedic Molecular Medicine and Applied Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio 43210, USA.

出版信息

Mol Ther. 2007 Aug;15(8):1543-50. doi: 10.1038/sj.mt.6300192. Epub 2007 May 22.

DOI:10.1038/sj.mt.6300192
PMID:17519894
Abstract

In articular fractures, both bone and cartilage are injured. We tested whether stem cells transduced with bone morphogenetic protein 2 (BMP2) can promote bone and cartilage repair. Distal femoral articular osteotomies in nude rats were treated with stem cells, either wild-type or transduced with an adenoviral (Ad) BMP2. Cells were delivered in alginate (ALG) carrier or by direct injection in saline solution. Gene expression of these cells at the osteotomy site was confirmed by in vivo imaging. At day 14, only the group that received AdBMP2 stem cells by direct injection showed completely healed osteotomies, while other groups remained unhealed (P < 0.0003). In ALG groups, bone healing was impeded by the development of a chondroid mass, most pronounced in the AdBMP2 ALG group (P < 0.002). We were successful in achieving repair of both bone and cartilage in vivousing direct stem cell injection. Our data suggests that BMP2 augmentation might be critically important in achieving this effect.

摘要

在关节骨折中,骨骼和软骨都会受到损伤。我们测试了用骨形态发生蛋白2(BMP2)转导的干细胞是否能促进骨骼和软骨修复。对裸鼠的股骨远端关节截骨术分别用野生型干细胞或用腺病毒(Ad)BMP2转导的干细胞进行治疗。细胞通过藻酸盐(ALG)载体递送或直接注射到盐溶液中。通过体内成像证实了这些细胞在截骨部位的基因表达。在第14天,只有通过直接注射接受AdBMP2干细胞的组显示截骨完全愈合,而其他组仍未愈合(P<0.0003)。在ALG组中,类软骨块的形成阻碍了骨愈合,在AdBMP2 ALG组中最为明显(P<0.002)。我们通过直接注射干细胞在体内成功实现了骨骼和软骨的修复。我们的数据表明,BMP2增强可能对实现这一效果至关重要。

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