De Luna Andrea, Otahal Alexander, Nehrer Stefan
Center for Regenerative Medicine, Department for Health Sciences, Medicine and Research, Danube University Krems, Krems an der Donau, Austria.
Front Cell Dev Biol. 2020 Dec 10;8:593386. doi: 10.3389/fcell.2020.593386. eCollection 2020.
As the world's population is aging, the incidence of the degenerative disease Osteoarthritis (OA) is increasing. Current treatment options of OA focus on the alleviation of the symptoms including pain and inflammation rather than on restoration of the articular cartilage. Cell-based therapies including the application of mesenchymal stromal cells (MSCs) have been a promising tool for cartilage regeneration approaches. Due to their immunomodulatory properties, their differentiation potential into cells of the mesodermal lineage as well as the plurality of sources from which they can be isolated, MSCs have been applied in a vast number of studies focusing on the establishment of new treatment options for Osteoarthritis. Despite promising outcomes and , applications of MSCs are connected with teratoma formation, limited lifespan of differentiated cells as well as rejection of the cells after transplantation, highlighting the need for new cell free approaches harboring the beneficial properties of MSCs. It has been demonstrated that the regenerative potential of MSCs is mediated by the release of paracrine factors rather than by differentiation into cells of the desired tissue. Besides soluble factors, extracellular vesicles are the major component of a cell's secretome. They represent novel mechanisms by which (pathogenic) signals can be communicated between cell types as they deliver bioactive molecules (nucleic acids, proteins, lipids) from the cell of origin to the target cell leading to specific biological processes upon uptake. This review will give an overview about extracellular vesicles including general characteristics, isolation methods and characterization approaches. Furthermore, the role of MSC-derived extracellular vesicles in and studies for cartilage regeneration will be summarized with special focus on transported miRNA which either favored the progression of OA or protected the cartilage from degradation. In addition, studies will be reviewed investigating the impact of MSC-derived extracellular vesicles on inflammatory arthritis. As extracellular vesicles are present in all body fluids, their application as potential biomarkers for OA will also be discussed in this review. Finally, studies exploring the combination of MSC-derived extracellular vesicles with biomaterials for tissue engineering approaches are summarized.
随着世界人口老龄化，退行性疾病骨关节炎（OA）的发病率正在上升。OA目前的治疗方案侧重于缓解包括疼痛和炎症在内的症状，而非恢复关节软骨。包括应用间充质基质细胞（MSCs）在内的基于细胞的疗法一直是软骨再生方法中一种有前景的工具。由于其免疫调节特性、向中胚层谱系细胞的分化潜能以及可从中分离的多种来源，MSCs已被应用于大量旨在建立OA新治疗方案的研究中。尽管取得了令人鼓舞的成果，但MSCs的应用与畸胎瘤形成、分化细胞寿命有限以及移植后细胞排斥有关，这突出表明需要新的无细胞方法来保留MSCs的有益特性。已经证明，MSCs的再生潜能是由旁分泌因子的释放介导而非通过分化为所需组织的细胞。除了可溶性因子外，细胞外囊泡是细胞分泌组的主要成分。它们代表了一种新的机制，通过这种机制，（致病）信号可以在细胞类型之间传递，因为它们将生物活性分子（核酸、蛋白质、脂质）从起源细胞传递到靶细胞，导致摄取后发生特定的生物学过程。本综述将概述细胞外囊泡，包括一般特征、分离方法和表征方法。此外，将总结MSCs来源的细胞外囊泡在软骨再生的体外和体内研究中的作用，特别关注所运输的微小RNA，其要么促进OA的进展，要么保护软骨免于降解。此外，还将综述研究MSCs来源的细胞外囊泡对炎性关节炎影响的研究。由于细胞外囊泡存在于所有体液中，它们作为OA潜在生物标志物的应用也将在本综述中进行讨论。最后，总结了探索MSCs来源的细胞外囊泡与生物材料用于组织工程方法相结合的研究。
