Velot Émilie, Madry Henning, Venkatesan Jagadeesh K, Bianchi Arnaud, Cucchiarini Magali
Faculté de Médecine, Biopôle de l'Université de Lorraine, Campus Brabois-Santé, Laboratoire UMR 7365 CNRS-Université de Lorraine, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine, Vandoeuvre-Lès-Nancy, France.
Campus Brabois-Santé, Laboratoire de Travaux Pratiques de Physiologie, Faculté de Pharmacie, Université de Lorraine, Vandoeuvre-Lès-Nancy, France.
Front Bioeng Biotechnol. 2021 Apr 23;9:645039. doi: 10.3389/fbioe.2021.645039. eCollection 2021.
"Extracellular vesicles" (EVs) is a term gathering biological particles released from cells that act as messengers for cell-to-cell communication. Like cells, EVs have a membrane with a lipid bilayer, but unlike these latter, they have no nucleus and consequently cannot replicate. Several EV subtypes (e.g., exosomes, microvesicles) are described in the literature. However, the remaining lack of consensus on their specific markers prevents sometimes the full knowledge of their biogenesis pathway, causing the authors to focus on their biological effects and not their origins. EV signals depend on their cargo, which can be naturally sourced or altered (e.g., cell engineering). The ability for regeneration of adult articular cartilage is limited because this avascular tissue is partly made of chondrocytes with a poor proliferation rate and migration capacity. Mesenchymal stem cells (MSCs) had been extensively used in numerous and preclinical animal models for cartilage regeneration, and it has been demonstrated that their therapeutic effects are due to paracrine mechanisms involving EVs. Hence, using MSC-derived EVs as cell-free therapy tools has become a new therapeutic approach to improve regenerative medicine. EV-based therapy seems to show similar cartilage regenerative potential compared with stem cell transplantation without the associated hindrances (e.g., chromosomal aberrations, immunogenicity). The aim of this short review is to take stock of occurring EV-based treatments for cartilage regeneration according to their healing effects. The article focuses on cartilage regeneration through various sources used to isolate EVs (mature or stem cells among others) and beneficial effects depending on cargos produced from natural or tuned EVs.
“细胞外囊泡”(EVs)是一个统称,涵盖从细胞中释放出来的生物颗粒,这些颗粒充当细胞间通讯的信使。与细胞一样,细胞外囊泡有一个带有脂质双层的膜,但与细胞不同的是,它们没有细胞核,因此无法复制。文献中描述了几种细胞外囊泡亚型(例如,外泌体、微囊泡)。然而,由于对其特定标志物仍缺乏共识,有时会妨碍对其生物发生途径的全面了解,导致作者们专注于它们的生物学效应而非其起源。细胞外囊泡的信号取决于其携带的物质,这些物质可以是天然来源的,也可以是经过改变的(例如,细胞工程改造)。成年关节软骨的再生能力有限,因为这种无血管组织部分由增殖率低和迁移能力差的软骨细胞组成。间充质干细胞(MSCs)已被广泛应用于众多临床前动物软骨再生模型中,并且已经证明它们的治疗效果归因于涉及细胞外囊泡的旁分泌机制。因此,使用源自间充质干细胞的细胞外囊泡作为无细胞治疗工具已成为改善再生医学的一种新治疗方法。与干细胞移植相比,基于细胞外囊泡的治疗似乎显示出相似的软骨再生潜力,且没有相关的障碍(例如,染色体畸变、免疫原性)。这篇简短综述的目的是根据其治疗效果,对目前基于细胞外囊泡的软骨再生治疗进行总结。本文重点关注通过用于分离细胞外囊泡的各种来源(包括成熟细胞或干细胞等)实现的软骨再生,以及取决于天然或经过调整的细胞外囊泡所产生的携带物质的有益效果。