Reparative homing of bone mesenchymal stem cells induced by iMSCs via the SDF-1/CXCR4 axis for articular cartilage defect restoration

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2024-11-13 DOI:10.1016/j.biopha.2024.117649

Gang Cheng , Xulei Wang , Feng Zhang , Kang Wang , Ying Li , Tingting Guo , Nuo Xu , Wei Wei , Shangxue Yan

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引用次数: 0

Abstract

Background

The intrinsic healing ability of articular cartilage is poor after injury or illness, and untreated injury could lead to cartilage degeneration and ultimately osteoarthritis. iMSCs are derived from embryonic induced pluripotent stem cells and have strong therapeutic capabilities in the repair of cartilage defects, while the mechanism of action is unclear. The aim of this study is to clarify the repair mode of iMSCs on cartilage defects in rat knee joints, elucidate the chemotactic effect of iMSCs on autologous BMSCs in rats, and provide a basis for the treatment of cartilage defects and endogenous regeneration with iMSCs.

Methods

Based on the establishment of the rat cartilage defect model, the reparative effect of iMSCs on the rat cartilage defect was evaluated. The cartilage repair was evaluated by quantitative score, H&E staining, Masson staining and Safranin-O staining, and the metabolic changes of iMSCs in the joint cavity were detected in vivo. The expression of SOX9, CD29, CD90, ColⅠ, ColⅡ, PCNA, SDF-1, and CXCR4 was detected by immunohistochemistry (IHC), IF, flow cytometry, respectively. After co-culturing iMSCs with BMSCs in vitro, the expression of CXCR4/SDF-1 on the cell membrane surface of BMSCs was detected by western blotting.; The level of p-Akt and p-Erk1/2 in total protein of BMSCs were detected by western blotting.

Significance

Our research results provide experimental evidence for the treatment of cartilage defects and endogenous regeneration with iMSCs; This also provides new ideas for the clinical treatment of cartilage defects using iMSCs.

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iMSCs 通过 SDF-1/CXCR4 轴诱导骨间充质干细胞修复归巢，用于关节软骨缺损修复。

背景：iMSCs来源于胚胎诱导多能干细胞，在修复软骨缺损方面具有很强的治疗能力，但其作用机制尚不清楚。本研究旨在阐明 iMSCs 对大鼠膝关节软骨缺损的修复模式，阐明 iMSCs 对大鼠自体 BMSCs 的趋化作用，为 iMSCs 治疗软骨缺损和内源性再生提供依据：方法：在建立大鼠软骨缺损模型的基础上，评估 iMSCs 对大鼠软骨缺损的修复作用。方法：在建立大鼠软骨缺损模型的基础上，评估了 iMSCs 对大鼠软骨缺损的修复效果，通过定量评分、H&E 染色、Masson 染色和 Safranin-O 染色对软骨修复效果进行了评估，并检测了 iMSCs 在关节腔内的代谢变化。免疫组织化学（IHC）、免疫荧光、流式细胞术分别检测了SOX9、CD29、CD90、ColⅠ、ColⅡ、PCNA、SDF-1和CXCR4的表达。在体外将 iMSCs 与 BMSCs 共同培养后，用 Western 印迹法检测 BMSCs 细胞膜表面 CXCR4/SDF-1 的表达；用 Western 印迹法检测 BMSCs 总蛋白中 p-Akt 和 p-Erk1/2 的水平：我们的研究结果为iMSCs治疗软骨缺损和内源性再生提供了实验证据，也为临床上利用iMSCs治疗软骨缺损提供了新思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.