State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
Department of Oral Implantology, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Luzhou, 646000, China.
Adv Healthc Mater. 2024 Aug;13(20):e2400257. doi: 10.1002/adhm.202400257. Epub 2024 Apr 2.
As newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs are obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructuring, the NTs surface is not only able to induce RAW264.7 for M2 polarization but also to generate more Migs formation, which can be internalized by following seeded mesenchymal stem cells (MSCs). Then, the NTs surface induced Migs are collected by density-gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity, and alizarin red staining, the osteogenic differentiation capacity of MSCs is significantly enhanced by Migs treatment, in line with the dosage. By RNA-sequence analysis, the enhancement of osteogenic differentiation is correlated with PI3K-AKT pathway activation that may originate from the M2 polarization state of donor cells. Finally, the Migs are coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis reveal that the Migs coated Ti implant shows significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration.
作为新发现的锚定在细胞外的基质的细胞外囊泡，迁移体（Migs）可能为操纵靶细胞的生物活性带来新的机会。在本研究中，通过二氧化钛纳米管表面（NTs）获得了 M2 巨噬细胞衍生的 Migs。由于纳米结构化的优势，NTs 表面不仅能够诱导 RAW264.7 细胞向 M2 极化，还能够产生更多的 Migs 形成，这些 Migs 可以被随后接种的间充质干细胞（MSCs）内化。然后，通过密度梯度离心从 NTs 表面收集诱导产生的 Migs，用于 MSCs 处理。免疫荧光染色、碱性磷酸酶活性和茜素红染色表明，Migs 处理显著增强了 MSCs 的成骨分化能力，且与剂量呈正相关。通过 RNA 测序分析，成骨分化的增强与 PI3K-AKT 通路的激活相关，该通路可能源自供体细胞的 M2 极化状态。最后，将 Migs 包被到 Ti 表面用于治疗应用。体外和体内分析均表明，包被 Migs 的 Ti 植入物显示出明显增强的成骨作用。总之，本研究表明纳米表面可能是 Migs 产生的有利平台，为组织再生带来了新的概念。
