Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model
Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model
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DOI：
10.1007/s002239900540
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发表时间：
1998-10-01
影响因子：
4.2
通讯作者：
Lou, J
中科院分区：
文献类型：
--
作者：
Riew, KD;Wright, NM;Lou, J
骨髓间充质干细胞是一种多潜能细胞，具有分化为骨祖细胞的能力。已有研究表明，BMP-2可以促进这一分化过程。为了延长BMP-2的转化效果，我们使用腺病毒。携带人骨形成蛋白-2基因的载体转导新西兰大白兔骨髓间充质干细胞。组织培养分析表明，这些细胞确实产生了BMP-2蛋白。这些被转导的干细胞随后被自体重新移植到供体兔体内。将细胞放置在5只兔的横突间区。在每五只兔中，就有一只产生了新骨，这在放射学和组织学检查中都是明显的。我们的结论是，有可能成功地转导BMP-2基因的骨髓间充质干细胞，使其在体外产生BMP-2蛋白。此外，转导导致这些细胞转化为能够在体内产生骨的骨祖细胞系。这些数据表明，使用重组腺病毒载体进行基因治疗作为促进脊柱融合的工具是可行的。进一步提高基因转移的保真度和寿命的工作是有必要的。
Bone marrow-derived mesenchymal stem cells are pluripotential cells that have the capacity to differentiate into an osteoprogenitor line. It has been demonstrated that BMP-2 can enhance this differentiation process. In an attempt to prolong the transforming effect of BMP-2, we used an adenoviral. vector carrying the human BMP-2 gene to transduce marrow-derived mesenchymal stem cells of New Zealand white rabbits. Assays on tissue culture demonstrated that these cells indeed produced the BMP-2 protein. These transduced stem cells were then autologously reimplanted into the donor rabbits. The cells were placed in the intertransverse process area of five rabbits. In one out of the five rabbits, this resulted in the production of new bone which was demonstrable on both radiographic and histologic examination. We conclude that it is possible to successfully transduce mesenchymal stem cells with the gene for BMP-2 such that these cells will produce the BMP-2 protein in vitro. Further, the transduction results in transformation of these cells into an osteoprogenitor line capable of producing bone in vivo. These data suggest the feasibility of employing gene therapy using recombinant adenoviral vectors as a tool for enhancing spine fusion. Further work to improve the fidelity and longevity of the gene transfer is warranted.