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鹿茸干细胞来源的外泌体修复机械性软骨损伤。

Repair of Mechanical Cartilage Damage Using Exosomes Derived from Deer Antler Stem Cells.

机构信息

Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, 130112 Changchun, Jilin, China.

The Scientific Research Center, China-Japan Union Hospital of Jilin University, 130033 Changchun, Jilin, China.

出版信息

Front Biosci (Landmark Ed). 2024 Aug 23;29(8):309. doi: 10.31083/j.fbl2908309.

DOI:10.31083/j.fbl2908309
PMID:39206920
Abstract

BACKGROUND

Articular cartilage has limited self-repair capacity, and current clinical treatment options for cartilage defects are inadequate. However, deer antler cartilage possesses unique regenerative properties, with the ability to rapidly repair itself. This rapid self-repair process is closely linked to the paracrine factors released by deer antler stem cells. These findings present potential for the development of cell-free therapies for cartilage defects in clinical settings. The aim of this study was to investigate a novel method for repairing cartilage.

METHODS

A rat model with articular cartilage defects was established through surgery. Hydrogels loaded with exosomes (Exos) derived from antler stem cells (ASC-Exos) were implanted into the rat cartilage defects. The extent of cartilage damage repair was assessed using histological methods. The effects of ASC-Exos on chondrocytes and rat bone marrow mesenchymal stem cells (BMSCs) were evaluated using cell viability assays, proliferation assays, and scratch assays. Additionally, the maintenance of the chondrocyte phenotype by ASC-Exos was assessed using real-time fluorescence quantitative PCR (qPCR) and western blot analysis. The protein components contained of the Exos were identified using data-independent acquisition (DIA) mass spectrometry.

RESULTS

ASC-Exos significantly promoted the repair of cartilage tissue damage. The level of cartilage repair in the experimental group (ASC-Exos) was higher than that in the positive control (human adipose-derived stem cells, hADSC-Exos) and negative control (dulbecco's modified eagle medium) groups ( < 0.05). experiments demonstrated that ASC-Exos significantly enhanced the proliferation abilities of chondrocytes and the proliferation abilities and the migration abilities of BMSCs ( < 0.05). ASC-Exos up-regulated the expression levels of Aggrecan, Collagen II (COLII), and Sox9 mRNA and proteins in chondrocytes. Analysis of ASC-Exos protein components revealed the presence of active components such as Serotransferrin (TF), S100A4, and Insulin-like growth factor-binding protein 1 (IGF1).

CONCLUSIONS

ASC-Exos have a significant effect on cartilage damage repair, which may be attributed to their promotion of chondrocyte and BMSCs proliferation and migration, as well as the maintenance of chondrocyte phenotype. This effect may be mediated by the presence of TF, S100A4, and IGF1.

摘要

背景

关节软骨自我修复能力有限,目前临床治疗软骨缺损的方法并不理想。然而,鹿茸软骨具有独特的再生特性,能够快速自我修复。这种快速自我修复过程与鹿茸干细胞分泌的旁分泌因子密切相关。这些发现为开发细胞游离治疗软骨缺损提供了潜在的可能性。本研究旨在探讨一种新的软骨修复方法。

方法

通过手术建立大鼠关节软骨缺损模型,将负载外泌体(Exos)的水凝胶(ASC-Exos)植入大鼠软骨缺损部位。采用组织学方法评估软骨损伤修复程度。通过细胞活力测定、增殖测定和划痕实验评估 ASC-Exos 对软骨细胞和大鼠骨髓间充质干细胞(BMSCs)的影响。此外,通过实时荧光定量 PCR(qPCR)和 Western blot 分析评估 ASC-Exos 对软骨细胞表型的维持。使用数据非依赖性采集(DIA)质谱法鉴定 Exos 中的蛋白成分。

结果

ASC-Exos 显著促进软骨组织损伤的修复。实验组(ASC-Exos)的软骨修复水平高于阳性对照组(人脂肪来源干细胞,hADSC-Exos)和阴性对照组(杜氏改良伊格尔培养基)(<0.05)。实验表明,ASC-Exos 显著增强了软骨细胞的增殖能力,以及 BMSCs 的增殖能力和迁移能力(<0.05)。ASC-Exos 上调了软骨细胞中 Aggrecan、Collagen II(COLII)和 Sox9 mRNA 和蛋白的表达水平。分析 ASC-Exos 蛋白成分发现,Serotransferrin(TF)、S100A4 和胰岛素样生长因子结合蛋白 1(IGF1)等活性成分的存在。

结论

ASC-Exos 对软骨损伤修复具有显著效果,这可能归因于其促进软骨细胞和 BMSCs 的增殖和迁移,以及维持软骨细胞表型。这种作用可能是由 TF、S100A4 和 IGF1 介导的。

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