Abstract：
Mesenchymal stem cells (MSCs) have been shown to exert a positive impact on osteonecrosis of the femoral head (ONFH) in preclinical experiments and clinical trials. After the femoral head suffers avascular necrosis, the transplanted MSCs undergo a great deal of stress-induced apoptosis and senescence in this microenvironment. So, survival and differentiation of MSCs in osteonecrotic areas are especially important in ONFH. Although MSCs and endothelial cells (ECs) co-culture enhancing proliferation and osteogenic differentiation of MSCs and form more mature vasculature in vivo, it remains unknown whether the co-culture cells are able to repair ONFH. In this study, we explored the roles and mechanisms of co-transplantation of angiotensin II (Ang II)-MSCs and ECs in repairing early ONFH. In vitro, when MSCs and ECs were co-cultured in a ratio of 5:1, both types of cells managed to proliferate and induce both osteogenesis and angiogenesis. Then, we established a rabbit model of steroid-induced ONFH and co-transplantation of Ang II-MSCs and ECs through the tunnel of core decompression. Four weeks later, histological and Western blot analyses revealed that ONFH treated with Ang II-MSCs and ECs may promote ossification and revascularization by increasing the expression of collagen type I, runt-related transcription factor 2, osteocalcin, and vascular endothelial growth factor in the femoral head. Our data suggest that co-transplantation of Ang II-MSCs and ECs was able to rescue the early steroid-induced ONFH via promoting osteogenesis and angiogenesis, which may be regarded as a novel therapy for the treatment of ONFH in a clinical setting.
摘要：
在临床前实验和临床试验中，间充质干细胞（MSC）已被证明对股骨头坏死（ONFH）产生积极影响。股骨头缺血性坏死后，移植的MSCs在这种微环境中经历了大量的应激诱导的凋亡和衰老。所以,在ONFH中，骨髓间充质干细胞在坏死区的存活和分化尤为重要。虽然MSCs和内皮细胞（ECs）共培养增强了MSCs的增殖和成骨分化，并在体内形成更成熟的脉管系统，目前尚不清楚共培养细胞是否能够修复ONFH。在这项研究中,我们探讨了血管紧张素II（AngII）-MSCs和ECs共同移植在修复早期ONFH中的作用和机制。体外，当MSCs和ECs以5:1的比例共培养时,两种类型的细胞都设法增殖并诱导成骨和血管生成。然后，我们建立了兔激素诱导的ONFH模型，并通过核减压通道将AngII-MSCs和ECs共同移植。四周后,组织学和蛋白质印迹分析显示，用AngII-MSCs和ECs处理的ONFH可能通过增加I型胶原的表达来促进骨化和血运重建。矮小相关转录因子2,骨钙蛋白,股骨头血管内皮生长因子。我们的数据表明AngII-MSCs和ECs的共同移植能够通过促进成骨和血管生成来挽救早期类固醇诱导的ONFH。这可能被认为是一种在临床上治疗ONFH的新疗法。
