Davidson Building, School of Molecular Biosciences, University of Glasgow, Glasgow G12 8QQ, UK;
School of Infection & Immunity, University of Glasgow, Glasgow G12 8QQ, UK.
Cells. 2023 Jun 23;12(13):1707. doi: 10.3390/cells12131707.
Extracellular vesicles (EVs), comprising microvesicles (MVs) and exosomes (Exos), are membranous vesicles secreted by cells which mediate the repair of cellular and tissue damage via paracrine mechanisms. The action of EVs under normative and morbid conditions in the context of ageing remains largely unexplored. We demonstrate that MVs, but not Exos, from Pathfinder cells (PCs), a putative stem cell regulatory cell type, enhance the repair of human dermal fibroblast (HDF) and mesenchymal stem cell (MSC) co-cultures, following both mechanical and genotoxic stress. Critically, this effect was found to be both cellular age and stress specific. Notably, MV treatment was unable to repair mechanical injury in older co-cultures but remained therapeutic following genotoxic stress. These observations were further confirmed in human dermal fibroblast (HDF) and vascular smooth muscle cell (VSMC) co-cultures of increasing cellular age. In a model of comorbidity comprising co-cultures of HDFs and highly senescent abdominal aortic aneurysm (AAA) VSMCs, MV administration appeared to be senotherapeutic, following both mechanical and genotoxic stress. Our data provide insights into EVs and the specific roles they play during tissue repair and ageing. These data will potentiate the development of novel cell-free therapeutic interventions capable of attenuating age-associated morbidities and avoiding undesired effects.
细胞外囊泡 (EVs) 包括微囊泡 (MVs) 和外泌体 (Exos)，是细胞分泌的膜性囊泡，通过旁分泌机制介导细胞和组织损伤的修复。EVs 在衰老背景下的正常和病态条件下的作用在很大程度上仍未被探索。我们证明，在机械和遗传毒性应激后，探路者细胞 (PCs) 即一种假定的干细胞调节细胞类型的 MVs，但不是 Exos，可增强人真皮成纤维细胞 (HDF) 和间充质干细胞 (MSC) 共培养物的修复。至关重要的是，这种效应既具有细胞年龄特异性，也具有应激特异性。值得注意的是，MV 处理不能修复老年共培养物的机械损伤，但在遗传毒性应激后仍具有治疗作用。这些观察结果在不断增加细胞年龄的人真皮成纤维细胞 (HDF) 和血管平滑肌细胞 (VSMC) 共培养物中得到了进一步证实。在包含 HDF 和高度衰老的腹主动脉瘤 (AAA) VSMC 共培养物的合并症模型中，MV 给药似乎在机械和遗传毒性应激后具有抗衰老作用。我们的数据提供了有关 EVs 及其在组织修复和衰老过程中特定作用的见解。这些数据将促进新型无细胞治疗干预措施的发展，这些措施能够减轻与年龄相关的疾病并避免不良影响。
