Katsube Kosuke, Bishop Allen T, Simari Robert D, Ylä-Herttuala Seppo, Friedrich Patricia F
Department of Orthopedic Surgery, Microvascular Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
J Orthop Res. 2005 Mar;23(2):469-74. doi: 10.1016/j.orthres.2004.08.013. Epub 2004 Nov 30.
Avascular necrosis of bone is a relatively common clinical condition caused by inflammatory conditions, steroid or other drug use, and trauma that affect many different sites in man. Revascularization of the necrotic bone is slow to occur, often resulting in bone resorption and eventual collapse of the involved bone. Rapid revascularization and subsequent bone remodeling may lead to improved outcomes. Surgical revascularization with arterovenous bundles (AV bundles) or vascularized bone grafts results in neoangiogenesis and bone remodeling. Gene transfer of an angiogenic factor to the vessel wall may be an additional strategy to further accelerate this process. In this study, we examined the effectiveness of vascular endothelial growth factor (VEGF) gene transfer to augment surgical revascularization of necrotic bone. An adenoviral vector, either with the VEGF gene (VEGF-A) or identical virus without the cDNA VEGF insert (ADV-DeltaE1) was used to transduce endothelial cells in rabbit saphenous arteries. The artery was then placed with its venae comitantes as an AV bundle into necrotic iliac crest bone in vivo. Angiogenesis in the necrotic bone was quantified by bone blood flow measurement and assessment of vessel density following microangiography. The extent of neoangiogenesis was significantly greater in the VEGF group than the control group at 1 week postoperatively.
骨缺血性坏死是一种相对常见的临床病症,由炎症性疾病、类固醇或其他药物使用以及外伤引起,可影响人体的许多不同部位。坏死骨的血管再生发生缓慢,常导致骨吸收以及受累骨骼最终塌陷。快速的血管再生和随后的骨重塑可能会带来更好的结果。采用动静脉束(AV束)或带血管蒂骨移植进行手术血管再生可导致新血管形成和骨重塑。将血管生成因子基因转移至血管壁可能是进一步加速这一过程的额外策略。在本研究中,我们检测了血管内皮生长因子(VEGF)基因转移增强坏死骨手术血管再生的有效性。使用携带VEGF基因的腺病毒载体(VEGF-A)或不含cDNA VEGF插入片段的相同病毒(ADV-DeltaE1)转导兔隐动脉中的内皮细胞。然后将该动脉及其伴行静脉作为AV束植入体内坏死的髂嵴骨中。通过测量骨血流量和微血管造影术后评估血管密度来量化坏死骨中的血管生成。术后1周时,VEGF组的新血管形成程度明显高于对照组。