Wen Q, Ma L, Chen Y-P, Yang L, Luo W, Wang X-N
Institute of Molecular Immunology, Southern Medical University, Guangzhou, People's Republic of China.
Gene Ther. 2008 Dec;15(23):1523-35. doi: 10.1038/gt.2008.110. Epub 2008 Jul 17.
The treatment of hormone-induced early-stage avascular necrosis of the femoral head (ANFH) with transplantation of hepatocyte growth factor (HGF)-transgenic bone marrow stromal stem cells (BMSCs) was examined. A rabbit model of hormone-induced early ANFH was first established. BMSCs were transplanted by core decompression under the guidance of computed tomography (CT). A supportive fibrinogen drug delivery mixture (FG) was tested for mechanical enhancement of stem cell delivery. Therapeutic efficacy was evaluated by CT, magnetic resonance imaging (MRI), CT perfusion imaging, ink artery infusion angiography, hematoxylin-and-eosin staining and immunohistochemical staining for extracellular signal-regulated kinase-1/2 of pathological sections. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving transplanted transgenic BMSCs with FG. Newly generated capillaries were visible on the bone plates of the trabeculae, and the bone marrow was rich in hematopoietic tissue. These results demonstrate that the combination of core decompression and transplantation of HGF transgenic autologous BMSCs enhanced blood vessel regeneration and bone reconstruction in the ANFH model. This study provides experimental data that motivate possible clinical use of this therapeutic strategy.
研究了采用肝细胞生长因子(HGF)转基因骨髓基质干细胞(BMSCs)移植治疗激素诱导的早期股骨头缺血性坏死(ANFH)。首先建立了激素诱导的早期ANFH兔模型。在计算机断层扫描(CT)引导下通过髓芯减压移植BMSCs。测试了一种支持性纤维蛋白原药物递送混合物(FG)对干细胞递送的机械增强作用。通过CT、磁共振成像(MRI)、CT灌注成像、墨汁动脉灌注血管造影、苏木精-伊红染色以及病理切片细胞外信号调节激酶-1/2的免疫组织化学染色来评估治疗效果。在接受FG移植的转基因BMSCs的动物中观察到小梁排列规则且有明显的骨再生。在小梁的骨板上可见新生毛细血管,骨髓富含造血组织。这些结果表明,髓芯减压与HGF转基因自体BMSCs移植相结合可增强ANFH模型中的血管再生和骨重建。本研究提供了实验数据,推动了这种治疗策略在临床上的可能应用。