Institute of Acoustics, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China.
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Tongji University, Shanghai, 200065, China.
Stem Cell Res Ther. 2023 Apr 17;14(1):93. doi: 10.1186/s13287-023-03296-6.
BACKGROUND: Mesenchymal stem cell (MSC) transplantation therapy is highly investigated for the regenerative repair of cartilage defects. Low-intensity pulsed ultrasound (LIPUS) has the potential to promote chondrogenic differentiation of MSCs. However, its underlying mechanism remains unclear. Here, we investigated the promoting effects and mechanisms underlying LIPUS stimulation on the chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further evaluated its regenerative application value in articular cartilage defects in rats. METHODS: LIPUS was applied to stimulate cultured hUC-MSCs and C28/I2 cells in vitro. Immunofluorescence staining, qPCR analysis, and transcriptome sequencing were used to detect mature cartilage-related markers of gene and protein expression for a comprehensive evaluation of differentiation. Injured articular cartilage rat models were established for further hUC-MSC transplantation and LIPUS stimulation in vivo. Histopathology and H&E staining were used to evaluate the repair effects of the injured articular cartilage with LIPUS stimulation. RESULTS: The results showed that LIPUS stimulation with specific parameters effectively promoted the expression of mature cartilage-related genes and proteins, inhibited TNF-α gene expression in hUC-MSCs, and exhibited anti-inflammation in C28/I2 cells. In addition, the articular cartilage defects of rats were significantly repaired after hUC-MSC transplantation and LIPUS stimulation. CONCLUSIONS: Taken together, LIPUS stimulation could realize articular cartilage regeneration based on hUC-MSC transplantation due to the inhibition of the TNF signaling pathway, which is of clinical value for the relief of osteoarthritis.
背景:间充质干细胞(MSC)移植疗法高度适用于软骨缺损的再生修复。低强度脉冲超声(LIPUS)具有促进间充质干细胞向软骨分化的潜力。然而,其潜在机制尚不清楚。在此,我们研究了 LIPUS 刺激对人脐带间充质干细胞(hUC-MSCs)软骨分化的促进作用及其潜在机制,并进一步评估了其在大鼠关节软骨缺损中的再生应用价值。
方法:LIPUS 被应用于体外刺激培养的 hUC-MSCs 和 C28/I2 细胞。免疫荧光染色、qPCR 分析和转录组测序用于检测基因和蛋白表达的成熟软骨相关标志物,以进行全面的分化评估。建立损伤的关节软骨大鼠模型,进行体内 hUC-MSC 移植和 LIPUS 刺激。组织病理学和 H&E 染色用于评估 LIPUS 刺激对损伤关节软骨的修复效果。
结果:结果表明,特定参数的 LIPUS 刺激有效促进了成熟软骨相关基因和蛋白的表达,抑制了 hUC-MSCs 中 TNF-α基因的表达,并在 C28/I2 细胞中表现出抗炎作用。此外,hUC-MSC 移植和 LIPUS 刺激后,大鼠的关节软骨缺损得到了显著修复。
结论:综上所述,由于抑制 TNF 信号通路,LIPUS 刺激可以实现基于 hUC-MSC 移植的关节软骨再生,这对于缓解骨关节炎具有临床价值。
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