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Abstract：
Recently, there has been growing interest in using cell therapy through core decompression (CD) to treat osteonecrosis of the femoral head (ONFH). Our study aimed to investigate the effectiveness and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in treating steroid-induced ONFH. We constructed a steroid-induced ONFH rabbit model as well as dexamethasone (Dex)-treated bone microvascular endothelial cells (BMECs) model of human femoral head. We injected hUCMSCs into the rabbit femoral head via CD. The effects of hUCMSCs on steroid-induced ONFH rabbit model and Dex-treated BMECs were evaluated via micro-CT, microangiography, histology, immunohistochemistry, wound healing, tube formation, and western blotting assay. Furthermore, we conducted single-cell RNA sequencing (scRNA-seq) to examine the characteristics of endothelial cells, the activation of signaling pathways, and inter-cellular communication in ONFH. Our data reveal that hUCMSCs improved the femoral head microstructure and bone repair and promoted angiogenesis in the steroid-induced ONFH rabbit model. Importantly, hUCMSCs improved the migration ability and angioplasty of Dex-treated BMECs by secreting COL6A2 to activate FAK/PI3K/AKT signaling pathway via integrin α1β1.
摘要：
最近,通过髓芯减压(CD)使用细胞疗法治疗股骨头坏死(ONFH)的兴趣日益浓厚.我们的研究目的是探讨人脐带间充质干细胞（hUCMSCs）治疗激素诱导的ONFH的有效性和机制。我们构建了类固醇诱导的ONFH兔模型以及地塞米松（Dex）处理的人股骨头骨微血管内皮细胞（BMECs）模型。我们通过CD将hUCMSCs注射到兔股骨头中。通过显微CT评估hUCMSCs对激素诱导的ONFH兔模型和Dex处理的BMECs的影响。微血管造影,组织学,免疫组织化学，伤口愈合，管形成,和蛋白质印迹分析。此外，我们进行了单细胞RNA测序（scRNA-seq）来检查内皮细胞的特征，信号通路的激活，以及ONFH中的蜂窝间通信。我们的数据表明，hUCMSCs改善了激素诱导的ONFH兔模型的股骨头微结构和骨修复，并促进了血管生成。重要的是,hUCMSCs通过分泌COL6A2通过整合素α1β1激活FAK/PI3K/AKT信号通路，改善Dex处理的BMECs的迁移能力和血管成形术。
