Department of Pathology, Johns Hopkins University, Baltimore, United States.
Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, China.
Elife. 2019 Sep 4;8:e48191. doi: 10.7554/eLife.48191.
The vascular wall is a source of progenitor cells that are able to induce skeletal repair, primarily by paracrine mechanisms. Here, the paracrine role of extracellular vesicles (EVs) in bone healing was investigated. First, purified human perivascular stem cells (PSCs) were observed to induce mitogenic, pro-migratory, and pro-osteogenic effects on osteoprogenitor cells while in non-contact co-culture via elaboration of EVs. PSC-derived EVs shared mitogenic, pro-migratory, and pro-osteogenic properties of their parent cell. PSC-EV effects were dependent on surface-associated tetraspanins, as demonstrated by EV trypsinization, or neutralizing antibodies for CD9 or CD81. Moreover, shRNA knockdown in recipient cells demonstrated requirement for the CD9/CD81 binding partners IGSF8 and PTGFRN for EV bioactivity. Finally, PSC-EVs stimulated bone repair, and did so via stimulation of skeletal cell proliferation, migration, and osteodifferentiation. In sum, PSC-EVs mediate the same tissue repair effects of perivascular stem cells, and represent an 'off-the-shelf' alternative for bone tissue regeneration.
血管壁是祖细胞的来源，这些祖细胞能够主要通过旁分泌机制诱导骨骼修复。在这里，研究了细胞外囊泡 (EVs) 在骨愈合中的旁分泌作用。首先，观察到纯化的人血管周干细胞 (PSC) 在非接触共培养时通过 EV 的分泌来诱导成骨前体细胞的有丝分裂、迁移和促成骨作用。PSC 衍生的 EV 具有其亲本细胞的有丝分裂、迁移和促成骨特性。PSC-EV 的作用依赖于表面相关的四跨膜蛋白，如 EV 胰蛋白酶处理或针对 CD9 或 CD81 的中和抗体所证明的那样。此外，受体细胞中的 shRNA 敲低表明需要 CD9/CD81 结合伴侣 IGSF8 和 PTGFRN 来实现 EV 的生物活性。最后，PSC-EVs 刺激骨修复，通过刺激骨骼细胞增殖、迁移和成骨分化来实现。总之，PSC-EVs 介导了血管周干细胞的相同组织修复作用，并且代表了用于骨组织再生的“现成”替代物。
