Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.
Translational Medicine Center, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221086965. doi: 10.1177/09636897221086965.
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 , 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. , 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.
间充质干细胞(MSCs)在临床前实验和临床试验中已被证明对股骨头坏死(ONFH)有积极影响。在股骨头发生缺血性坏死后,移植的 MSCs 在这种微环境中经历大量应激诱导的细胞凋亡和衰老。因此,MSCs 在骨坏死区域的存活和分化在 ONFH 中尤为重要。尽管 MSC 和内皮细胞(ECs)共培养可以增强 MSCs 的增殖和成骨分化并形成更成熟的血管,但尚不清楚共培养细胞是否能够修复 ONFH。在这项研究中,我们探讨了共转染血管紧张素 II(Ang II)-MSCs 和 ECs 在修复早期 ONFH 中的作用和机制。当 MSCs 和 ECs 以 5:1 的比例共培养时,两种类型的细胞都能够增殖并诱导成骨和血管生成。然后,我们通过核心减压隧道建立了兔激素诱导的 ONFH 模型,并共转染 Ang II-MSCs 和 ECs。四周后,组织学和 Western blot 分析表明,Ang II-MSCs 和 ECs 处理的 ONFH 可能通过增加股骨头中 I 型胶原、Runt 相关转录因子 2、骨钙素和血管内皮生长因子的表达来促进成骨和血管再生。我们的数据表明,共转染 Ang II-MSCs 和 ECs 能够通过促进成骨和血管生成来挽救早期激素诱导的 ONFH,这可能被视为临床治疗 ONFH 的一种新疗法。