Department of Sports Medicine, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China.
Department of Sports Medicine, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China.
Acta Biomater. 2021 Apr 15;125:253-266. doi: 10.1016/j.actbio.2021.02.039. Epub 2021 Feb 28.
Direct implantation of mesenchymal stem cells (MSCs) for cartilage and bone tissue engineering faces challenges, such as immune rejection and loss of cellular viability or functionality. As nanoscale natural particles, exosomes or small extracellular vesicles (EVs) of MSCs have potential to circumvent these problems. It is significant to investigate the impact of the tissue origin of MSCs on the therapeutic bioactivity of their corresponding EVs for cartilage and bone regeneration. Here, rat MSCs isolated from the adipose, bone marrow, and synovium are cultured to obtain their corresponding EVs (ADSC-EVs, BMSC-EVs, and SMSC-EVs, respectively). The ADSC-EVs stimulate the migration, proliferation, and chondrogenic and osteogenic differentiation of BMSCs in vitro as well as cartilage and bone regeneration in a mouse model more than the BMSC-EVs or SMSC-EVs. Proteomics analysis reveals that the tissue origin contributes to the distinct protein profiles among the three types of EVs, which induced cartilage and bone regenerative capacities by potential mechanisms of regulating signaling pathways including focal adhesion, ECM-receptor interaction, actin cytoskeleton, cAMP, and PI3K-Akt signaling pathways. Consequently, these findings provide insight that the adipose may be a superior candidate in EV-based nanomedicine for cartilage and bone regeneration. STATEMENT OF SIGNIFICANCE: Extracelluar vesicles (EVs) of mesenchymal stem cells (MSCs) have been considered as a promising approach in cartilage and bone tissue engineering. In this study, for the first time, we investigated the tissue origin effect of EVs on chondrogenesis and osteogenesis of MSCs in vitro and in vivo. The results demonstrated that EVs of adipose-derived MSCs showed the most efficiency. Meanwhile, protein proteomics revealed the potential mechanisms. We provide a novel evidence that the adipose is a superior reservoir in EV-based nanotechnologies and biomaterials for cartilage and bone regeneration.
间充质干细胞（MSCs）的直接植入在软骨和骨组织工程中面临挑战，例如免疫排斥和细胞活力或功能丧失。作为纳米级天然颗粒，MSCs 的外泌体或小细胞外囊泡（EVs）具有规避这些问题的潜力。研究 MSCs 的组织来源对其相应 EVs 在软骨和骨再生中的治疗生物活性的影响具有重要意义。在这里，从脂肪、骨髓和滑膜中分离大鼠 MSCs 进行培养，以获得相应的 EV（ADSC-EVs、BMSC-EVs 和 SMSC-EVs）。ADSC-EVs 刺激 BMSCs 的迁移、增殖以及体外软骨和成骨分化，以及在小鼠模型中的软骨和骨再生，比 BMSC-EVs 或 SMSC-EVs 更显著。蛋白质组学分析表明，组织来源导致三种 EV 之间存在明显的蛋白谱差异，这些 EV 通过调节包括粘着斑、细胞外基质受体相互作用、肌动蛋白细胞骨架、cAMP 和 PI3K-Akt 信号通路在内的信号通路，诱导软骨和骨再生能力。因此，这些发现提供了一种见解，即脂肪组织可能是基于 EV 的纳米医学在软骨和骨再生方面的一个更优候选。
声明意义：间充质干细胞（MSCs）的细胞外囊泡（EVs）已被认为是软骨和骨组织工程的一种很有前途的方法。在这项研究中，我们首次研究了 EVs 在 MSC 的体外和体内软骨生成和成骨中的组织来源效应。结果表明，脂肪来源的 MSC 的 EV 显示出最高的效率。同时，蛋白质蛋白质组学揭示了潜在的机制。我们提供了新的证据，表明脂肪组织是基于 EV 的纳米技术和生物材料在软骨和骨再生方面的优越来源。
