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骨再生和血管生成通过共移植预处理的间充质干细胞和内皮细胞血管紧张素 II 在早期类固醇诱导的股骨头坏死。

Bone Regeneration and Angiogenesis by Co-transplantation of Angiotensin II-Pretreated Mesenchymal Stem Cells and Endothelial Cells in Early Steroid-Induced Osteonecrosis of the Femoral Head.

机构信息

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.

出版信息

Cell Transplant. 2022 Jan-Dec;31:9636897221086965. doi: 10.1177/09636897221086965.

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 , 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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8401/8943589/bea86d57f590/10.1177_09636897221086965-fig1.jpg

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