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骨髓间充质干细胞分泌组增加马关节软骨细胞胶原积累及其迁移能力。

Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities.

机构信息

Normandie University, Unicaen, Biotargen, F-14000 Caen, France.

Molecular Engineering and Articular Physiopathology (IMoPA), French National Center for Scientific Research (CNRS), Université de Lorraine, F-54000 Nancy, France.

出版信息

Int J Mol Sci. 2022 May 21;23(10):5795. doi: 10.3390/ijms23105795.

Abstract

Equine osteoarthritis (OA) leads to cartilage degradation with impaired animal well-being, premature cessation of sport activity, and financial losses. Mesenchymal stem cell (MSC)-based therapies are promising for cartilage repair, but face limitations inherent to the cell itself. Soluble mediators and extracellular vesicles (EVs) secreted by MSCs are the alternatives to overcome those limitations while preserving MSC restorative properties. The effect of equine bone marrow MSC secretome on equine articular chondrocytes (eACs) was analyzed with indirect co-culture and/or MSC-conditioned media (CM). The expression of healthy cartilage/OA and proliferation markers was evaluated in eACs (monolayers or organoids). In vitro repair experiments with MSC-CM were made to evaluate the proliferation and migration of eACs. The presence of nanosized EVs in MSC-CM was appraised with nanoparticle tracking assay and transmission electron microscopy. Our results demonstrated that the MSC secretome influences eAC phenotype by increasing cartilage functionality markers and cell migration in a greater way than MSCs, which could delay OA final outcomes. This study makes acellular therapy an appealing strategy to improve equine OA treatments. However, the MSC secretome contains a wide variety of soluble mediators and small EVs, such as exosomes, and further investigation must be performed to understand the mechanisms occurring behind these promising effects.

摘要

马的骨关节炎(OA)导致软骨退化,动物福利受损,运动活动过早停止,经济损失。基于间充质干细胞(MSC)的治疗方法对软骨修复很有前途,但存在细胞本身固有的局限性。MSC 分泌的可溶性介质和细胞外囊泡(EVs)是克服这些局限性的替代方法,同时保留 MSC 的修复特性。通过间接共培养和/或 MSC 条件培养基(CM)分析了马骨髓 MSC 分泌组对马关节软骨细胞(eAC)的影响。在 eAC(单层或类器官)中评估了健康软骨/OA 和增殖标志物的表达。用 MSC-CM 进行了体外修复实验,以评估 eAC 的增殖和迁移。用纳米颗粒跟踪分析和透射电子显微镜评估了 MSC-CM 中纳米级 EV 的存在。我们的研究结果表明,MSC 分泌组通过增加软骨功能标志物和细胞迁移的方式影响 eAC 表型,这可能会延迟 OA 的最终结果。这项研究使无细胞治疗成为改善马 OA 治疗的一种有吸引力的策略。然而,MSC 分泌组包含各种可溶性介质和小 EVs,如外泌体,必须进一步研究以了解这些有前途的效果背后发生的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3664/9146805/762bb928ae2f/ijms-23-05795-g001.jpg

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