Migration and phenotype switching of macrophages at early-phase of bone-formation by secretomes from bone marrow derived mesenchymal stem cells using rat calvaria bone defect model.
Migration and phenotype switching of macrophages at early-phase of bone-formation by secretomes from bone marrow derived mesenchymal stem cells using rat calvaria bone defect model.
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DOI：
10.1016/j.jds.2021.08.012
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发表时间：
2022-01
影响因子：
3.5
通讯作者：
Kobayashi T
中科院分区：
文献类型：
--
作者：
Katagiri W;Takeuchi R;Saito N;Suda D;Kobayashi T
骨髓间充质干细胞（mesenchymal stem cells，MSCs）的条件培养液中含有多种细胞因子、趋化因子等分泌物。我们先前报道了骨髓源性间充质干细胞（MSC-CM）的条件培养基促进骨形成。最近，巨噬细胞表型从促炎M1型转换为抗炎M2型已被报道为组织再生过程中的重要现象。一些研究报道，这种表型转换是由分泌体调节的。在这项研究中，巨噬细胞表型在骨形成MSC-CM进行了研究。在无血清培养基中培养人MSC（hMSC），收集的培养基定义为MSC-CM。实时定量聚合酶链反应检测与MSC-CM共同培养的hMSCs中巨噬细胞相关基因的表达。将MSC-CM植入大鼠颅骨缺损模型，进行micro-CT和免疫组化评价。植入后2周和4周，MSC-CM组显示出增强的骨再生。C-C基序趋化因子2（CCL 2）、集落刺激因子2（CSF 2）和CD 163的基因表达在暴露于MSC-CM的细胞中显著上调。免疫组织化学染色显示，植入后72 h，MSC-CM组iNOS阳性M1巨噬细胞减少，而CD 204阳性M2巨噬细胞增加，M2/M1比值仅在MSC-CM组增加。MSC-CM增强巨噬细胞迁移，并在骨生成的早期阶段诱导M1型至M2型巨噬细胞转换。这种表型转换为血管生成、细胞迁移和骨生成提供了有利的环境，并有助于MSC-CM诱导的早期骨形成。
Conditioned media of cultured mesenchymal stem cells (MSCs) contain numerous kinds of secretomes such as cytokines and chemokines. We previously reported that conditioned media of bone marrow-derived MSCs (MSC-CM) promote bone formation. Recently, macrophage phenotype switching from the pro-inflammatory M1 type to the anti-inflammatory M2 type has been reported to be an important phenomenon during tissue regeneration. Some studies reported that this phenotype switching is regulated by secretomes. In this study, macrophage phenotype during bone formation by MSC-CM was investigated. Human MSCs (hMSCs) were cultured in serum-free medium and the collected medium was defined as MSC-CM. Macrophage-related gene expressions in hMSCs cultured with MSC-CM were evaluated by quantitative real-time polymerase chain reaction. MSC-CM was implanted and the evaluations by micro-CT and immunohistochemistry were performed using a rat the calvaria bone defect model. Two and four weeks after implantation, the MSC-CM group demonstrated enhanced bone regeneration. Gene expressions of C–C motif chemokine 2 (CCL2), colony-stimulating factor 2 (CSF2) and CD163 was significantly upregulated in cells exposed to MSC-CM. Immunohistochemical staining revealed that iNOS-positive M1 macrophages were reduced, while CD204-positive M2 macrophages were increased in the MSC-CM group at 72 h after implantation, and the M2/M1 ratio increased only in the MSC-CM group. MSC-CM enhances macrophage migration and induces M1 to M2 type macrophage switching at an early stage of osteogenesis. Such phenotype switching provides a favorable environment for angiogenesis, cellular migration, and osteogenesis and contributes to MSC-CM-induced early bone formation.
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影响因子：
4.3
作者：
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