Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy
Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy
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DOI：
10.1016/j.biomaterials.2003.11.038
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发表时间：
2004-08-01
期刊：
影响因子：
14
通讯作者：
Jimbow, K
中科院分区：
文献类型：
--
作者：
Ono, I;Yamashita, T;Jimbow, K
近年来，羟基磷灰石（HAP）作为骨替代材料的临床意义越来越明显，骨形态发生蛋白（BMP）作为一种诱导成骨的物质也越来越受到人们的关注。在这项研究中，在兔颅骨上形成直径为1.2cm的骨缺损，在止血完成后，用多孔HAP导入BMP-2基因（cDNA质粒），并对所产生的骨形成进行组织病理学分析。比较BMP-2 cDNA质粒不与阳离子脂质体作为载体组合的成骨量。对四组家兔进行了比较。在HAP组中，用含有40 μ g脂质体和假基因（PU）的HAP治疗颅骨缺损。BMP基因HAP组用浸泡在脂质体中的HAP和10 μ g BMP-2基因处理。另外，一组接受基因治疗，但不植入HAP。术后3、6、9周分别行X线片和组织病理学检查，观察颅骨缺损区骨形成情况。术后3周，在接受BMP-2基因而没有HAP的组中，颅骨缺损中有活跃的骨形成，并且在9周时观察到完全骨化。在接受含有BMP-2基因的HAP的组中，尽管在术后3周在支架周围有明显的新骨形成，但即使在术后9周，诱导的骨组织也没有填充支架的所有孔隙。这些结果证实了骨形成基因治疗的临床实用性，使用BMP-2基因与阳离子脂质体组合作为载体。有可能通过使基因治疗用支架的微观结构特化来改善BMP-2基因的施用效果。(C)2003 Elsevier Ltd.保留所有权利。
The clinical significance of hydroxyapatite (HAP) as a bone substitute has become apparent in recent years and bone morphogenetic protein (BMP) a substance which induces bone has attracted much attention. In this study, a 1.2 cm diameter bone defects created on rabbit cranium were treated with the BMP-2 gene (cDNA plasmid) introduced with porous HAP after completion of hemostasis and the resultant bone formation was analyzed histpathologically. The amounts of bone formation was compared BMP-2 cDNA plasmids were not combined with cationic liposomes as a vector. Four groups of rabbits were compared. In the HAP group the cranial bone defect was treated with HAP containing 40 mug of liposomes and a dummy gene (PU). The BMP gene HAP group was treated with HAP soaked in liposomes and 10mug of the BMP-2 gene. In addition, a group was treated with the gene without implanting HAP. Bone formation on the cranial defects was evaluated 3, 6 and 9 weeks after the operation, by X-ray and histopathological examinations. Three weeks after the operation there was Vigorous bone formation in the cranial defect in the group which received the BMP-2 gene without HAP, and complete ossification was observed at 9 weeks. In the group which received HAP containing the BMP-2 gene, although new bone formation was evident surrounding the scaffold 3 weeks post-operation, the induced bone tissue did not fill all the pores of the scaffold even at 9 weeks post-operation. These results confirm the clinical usefulness of gene therapy for bone formation, using the BMP-2 gene combined with cationic liposomes as a vector. It is possible that the effects of administering the BMP-2 gene will be improved by specializing the microstructure of scaffold for gene therapy. (C) 2003 Elsevier Ltd. All rights reserved.