Secretomes of mesenchymal stem cells induce early bone regeneration by accelerating migration of stem cells

Secretomes of mesenchymal stem cells induce early bone regeneration by accelerating migration of stem cells
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DOI:
10.1016/j.ajoms.2018.04.002
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发表时间:
2018-09-01
影响因子:
0.4
通讯作者:
Katagiri, Wataru
Katagiri, Wataru
中科院分区:
其他
文献类型:
--
作者:
Ogata, Kenichi;Osugi, Masashi;Katagiri, Wataru

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目的:我们以前报道过,来自人骨髓间充质干细胞(MSC-CM)的分泌物具有很强的促进骨再生的潜力。骨再生最重要的初始步骤是骨祖细胞迁移到骨缺损处。我们推测MSC-CM可以促进内源性干细胞更早地迁移到局部病变部位。在这项研究中,我们研究了MSC-CM通过加速大鼠颅骨骨缺损模型中的细胞迁移来诱导体内早期骨再生的潜力。材料和方法:进行细胞因子阵列分析以评估MSC-CM中包含的细胞因子类型。在大鼠颅骨中制造骨缺损(直径5 mm),并在受损区域植入悬浮在MSC-CM或磷酸盐缓冲盐水中的去端胶原。2周和4周后,进行放射学和组织学分析。用亲脂性示踪剂1,1-双十八烷基-3,3,3,3-四甲基吲哚三羰花青碘化物(DiR)标记大鼠间充质干细胞(rMSCs),并在注射DiR标记的rMSCs后的不同时间用体内成像技术对大鼠进行拍照。MSC-CM植入组大鼠颅骨骨再生最早。在MSC-CM植入组中,在注射后的前24 h内,使用体内成像观察标记的rMSCs从尾部向MSC-CM植入处的颅骨迁移。结论:MSC-CM可促进内源性干细胞的迁移,促进早期骨再生。
Objective: We previously reported that secretomes from human bone marrow-derived mesenchymal stem cells (MSC-CM) have a strong potential to accelerate bone regeneration. The most important initial step for bone regeneration is osteoprogenitor cell migration to bone defects. We hypothesized that MSC-CM enhance the migration of endogenous stem cells earlier to the local lesioned part. In this study, we investigated the potential of MSC-CM to induce in vivo early bone regeneration by accelerating cell migration in a rat calvarial bone defect model.Materials and methods: Cytokine array analysis was performed to assess the types of cytokines included in MSC-CM. Bone defects (5 mm in diameter) were created in the calvarial bones of rats, and the damaged areas were implanted with atelocollagen suspended in MSC-CM or phosphate buffered saline. After 2 and 4 weeks, radiographic and histological analyses were performed. Furthermore, rat mesenchymal stem cells (rMSCs) were labeled with the lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR), and the rats were photographed at various times after injection of the DiR-labeled rMSCs using in vivo imaging.Results: MSC-CM contained many factors with respect to cell migration and tissue regeneration. Bone regeneration in rat calvaria was observed earliest in the MSC-CM implantation group. Migration of the labeled rMSCs from the tail toward the calvaria, where MSC-CM was implanted, was observed during the first 24 h after injection in the MSC-CM implantation group using in vivo imaging. Immunohistochemistry also indicated early cell migration.Conclusion: MSC-CM enhanced the migration of endogenous stem cells facilitating earlier bone regeneration.