Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, 100081, China.
South China Center of Craniofacial Stem Cell Research, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510080, China.
J Extracell Vesicles. 2022 Jun;11(7):e12240. doi: 10.1002/jev2.12240.
Apoptotic vesicles (apoVs) are apoptotic cell-derived nanosized vesicles that play a crucial role in multiple pathophysiological settings. However, their detailed characteristics, specific surface markers, and biological properties are not fully elucidated. In this study, we compared mesenchymal stem cell (MSC)-derived apoVs and exosomes from three different types of MSCs including human bone marrow MSCs (hBMSCs), human adipose MSCs (hASCs), and mouse bone marrow MSCs (mBMSCs). We established a unique protein map of MSC-derived apoVs and identified the differences between apoVs and exosomes in terms of functional protein cargo and surface markers. Furthermore, we identified 13 proteins specifically enriched in apoVs compared to exosomes, which can be used as apoV-specific biomarkers. In addition, we showed that apoVs inherited apoptotic imprints such as Fas to ameliorate haemophilia A in factor VIII knockout mice via binding to the platelets' FasL to activate platelet functions, and therefore rescuing the blood clotting disorder. In summary, we systemically characterized MSC-derived apoVs and identified their therapeutic role in haemophilia A treatment through a previously unknown Fas/FasL linkage mechanism.
凋亡小体（apoVs）是由凋亡细胞衍生的纳米级小体，在多种病理生理状态中发挥着关键作用。然而，其详细特征、特定表面标志物和生物学特性尚未完全阐明。在这项研究中，我们比较了三种不同类型间充质干细胞（MSC）来源的凋亡小体和外泌体，包括人骨髓间充质干细胞（hBMSCs）、人脂肪间充质干细胞（hASCs）和鼠骨髓间充质干细胞（mBMSCs）。我们建立了 MSC 来源的凋亡小体的独特蛋白质图谱，并在功能蛋白货物和表面标志物方面比较了凋亡小体和外泌体之间的差异。此外，我们还鉴定出 13 种在凋亡小体中特异性富集的蛋白质，这些蛋白质可作为凋亡小体特异性生物标志物。此外，我们还表明，凋亡小体继承了凋亡印记，如 Fas，通过与血小板上的 FasL 结合来激活血小板功能，从而改善因子 VIII 敲除小鼠的血友病 A，从而纠正血液凝结障碍。总之，我们系统地描述了 MSC 来源的凋亡小体，并通过以前未知的 Fas/FasL 连接机制，鉴定出其在血友病 A 治疗中的治疗作用。
