Evaluation of BMP-2 gene-activated muscle grafts for cranial defect repair.

Evaluation of BMP-2 gene-activated muscle grafts for cranial defect repair.
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DOI:
10.1002/jor.22038
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发表时间:
2012-07
影响因子:
2.8
通讯作者:
Evans, Christopher H.
Evans, Christopher H.
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Fangjun;Porter, Ryan M.;Wells, James;Glatt, Vaida;Pilapil, Carmencita;Evans, Christopher H.

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大的、骨性的、节段性的缺损愈合不良。当暴露于成骨刺激物时,肌肉具有形成骨的倾向,所述成骨刺激物例如由编码骨形态发生蛋白-2(BMP-2)的cDNA的转移和表达提供的成骨刺激物。本研究评估了转基因的自体肌肉修复大鼠颅骨大缺损的能力。从股二头肌上切取8 mm × 2 mm的自体移植物,术中分别转染含人BMP-2或绿色荧光蛋白cDNA的重组腺病毒。当肌肉活检与载体一起孵育时,在同一动物的颅骨中手术产生中央顶骨8 mm缺损。然后将基因激活的肌肉移植物植入颅骨缺损处。8周后,对颅骨进行放射学、组织学、微型计算机断层扫描和双能X线吸收测定法检查。虽然在这段时间内没有一个缺损完全愈合,但表达BMP-2的肌肉移植物沉积的新骨是对照组的两倍多。组织学证实了新形成骨的解剖完整性,其厚度和矿物质密度与原始颅骨相当。这项研究证实了转基因肌肉的体内成骨特性,并提出了新的骨愈合策略。
Large, osseous, segmental defects heal poorly. Muscle has a propensity to form bone when exposed to an osteogenic stimulus such as that provided by transfer and expression of cDNA encoding bone morphogenetic protein-2 (BMP-2). The present study evaluated the ability of genetically modified, autologous muscle to heal large cranial defects in rats. Autologous grafts (8mm × 2mm) were punched from the biceps femoris muscle and transduced intraoperatively with recombinant adenovirus vector containing human BMP-2 or green fluorescent protein cDNA. While the muscle biopsies were incubating with the vector, a central parietal 8mm defect was surgically created in the calvarium of the same animal. The gene-activated muscle graft was then implanted into the cranial defect. After 8 weeks, crania were examined radiographically, histologically, and by micro-computed tomography and dual energy X-ray absorptiometry. Although none of the defects were completely healed in this time, muscle grafts expressing BMP-2 deposited more than twice as much new bone as controls. Histology confirmed the anatomical integrity of the newly formed bone, which was comparable in thickness and mineral density to the original cranial bone. This study confirms the in vivo osteogenic properties of genetically modified muscle and suggests novel strategies for healing bone.
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