Li Guangwen, Zhang Yan, Wang Haochen, Zhao Yuqi, Liu Kexin, Li Zhe, Meng Meng, He Yide, Song Wen
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, National Clinical Research Center for Oral Diseases, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Department of Oral Implantology, The Affiliated Stomatological Hospital, Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, 646000, Sichuan, China.
J Nanobiotechnology. 2025 Aug 29;23(1):592. doi: 10.1186/s12951-025-03641-2.
The regulatory role of migrasomes (Migs) has attracted growing attentions recently. However, most of the reports only focus on the influence of donor cells on Migs contents, regarding the substrate information. In the present study, the bone marrow mesenchymal stem cells (BMSCs) derived Migs were investigated on titania micropits/nanotubes (MNT) under different anodization voltages. The Migs formation was dependent on nanotubes dimensions, which was the most dominant on MNT5 (anodization under 5 V) surface and in line with ITGA5 expression level. The cargo analysis revealed significant enrichment of chemotaxis, in which the CXCL12 and CCL2 were the top enriched. Afterwards, the Migs could induce similar chemotaxis effect of CXCL12/CXCR4 axis in BMSCs and ECs and CCL2/CCR2 axis in macrophages. Further, the engulfment of Migs could induce significant enhancement of BMSCs osteogenic differentiation, ECs tube formation and macrophages M2 polarization. The in vivo ectopic bone formation model was subcutaneous implantation of biphasic calcium phosphate (BCP)/acylated methacrylate gelatin (GelMA) composite hydrogel with or without Migs. The scaffold could induce abundant cells recruitment 7 days post implantation and the CD90 or CD31 cell populations were significantly increased in the presence of Migs. After implantation for 2 and 4 weeks, the new bone growth within scaffold was significantly increased by Migs incorporation, both around BCP backbone and in the space area. In addition, the new bone area showed significant upregulation of CD163, CD31 and OSX. In conclusion, the titania nanotubes induced Migs from BMSCs could both recruit regenerative cells and directly promote osteogenesis, which may represent a new type of therapeutic EVs in bone tissue engineering.
迁移小体（Migs）的调节作用近来受到越来越多的关注。然而，大多数报告仅关注供体细胞对Migs内容物的影响，而涉及底物信息的较少。在本研究中，研究了在不同阳极氧化电压下，源自骨髓间充质干细胞（BMSCs）的Migs在二氧化钛微坑/纳米管（MNT）上的情况。Migs的形成取决于纳米管尺寸，这在MNT5（5V阳极氧化）表面最为显著，且与整合素α5（ITGA5）表达水平一致。货物分析显示趋化作用显著富集，其中CXC趋化因子配体12（CXCL12）和C-C基序趋化因子配体2（CCL2）富集程度最高。随后，Migs可在BMSCs和内皮细胞（ECs）中诱导CXCL12/CXCR4轴类似的趋化作用，在巨噬细胞中诱导CCL2/CCR2轴类似的趋化作用。此外，Migs的吞噬可显著增强BMSCs的成骨分化、ECs的管腔形成和巨噬细胞的M2极化。体内异位骨形成模型是皮下植入含或不含Migs的双相磷酸钙（BCP）/甲基丙烯酰化明胶（GelMA）复合水凝胶。植入后7天，支架可诱导大量细胞募集，且在有Migs存在时，CD90或CD31细胞群体显著增加。植入2周和4周后，通过掺入Migs，支架内的新骨生长显著增加，在BCP主干周围和空间区域均如此。此外，新骨区域的CD163、CD31和osterix（OSX）显著上调。总之，二氧化钛纳米管诱导BMSCs产生的Migs既能募集再生细胞，又能直接促进成骨，这可能代表了骨组织工程中一种新型的治疗性细胞外囊泡。
