The mutual effects between macrophages and cartilage templates in the process of subcutaneous endochondral bone formation.
The mutual effects between macrophages and cartilage templates in the process of subcutaneous endochondral bone formation.
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皮下软骨内骨形成过程中巨噬细胞与软骨模板的相互作用
DOI：
10.1039/c8ra04463e
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发表时间：
2018-06-27
期刊：
影响因子：
3.9
通讯作者：
Wang, Yining
中科院分区：
文献类型：
--
作者：
Huang, Jing;Zhou, Yi;Wang, Yan;Cai, Xinjie;Wang, Yining
植入物和受体免疫环境之间的相互作用是骨组织工程长期有效的关键。在本研究中，我们旨在研究巨噬细胞和软骨模板在皮下成骨过程中的相互作用。将原代小鼠骨髓间充质干细胞接种于明胶海绵中，体外软骨培养4周，形成软骨模板。然后将这些构建物植入单核细胞枯竭小鼠或正常C57BL/6小鼠的皮下。两个月后收获的植入物显示，与正常小鼠相比，单核细胞枯竭小鼠的成骨质量较差。在正常小鼠中，与空海绵相比，软骨模板招募了高比例的交替激活的巨噬细胞(CAM或M2)和经典激活的巨噬细胞(AAM或M1)。巨噬细胞与软骨模板的体外共培养实验也表明，软骨模板使巨噬细胞极化为M2表型，且这种作用甚至比原代BMSCs更强。反过来，极化的巨噬细胞与软骨模板共培养表明，与M0或M2相比，M1显著增加了软骨模板的成骨和血管生成标志的表达。这些数据表明，巨噬细胞在软骨模板的成骨过程中似乎是不可或缺的，并且软骨模板具有良好的免疫调节能力，使巨噬细胞极化为M2表型。M1是促进软骨模板成骨和血管生成的巨噬细胞的主要表型。巨噬细胞和软骨模板协同作用实现软骨内成骨。
The interplay between implants and the recipient immune environment is key to the long-term effectiveness of bone tissue engineering. In this study, we aimed to investigate the mutual effects between macrophages and cartilage templates in the process of subcutaneous osteogenesis. Primary mice bone marrow derived mesenchymal stem cells (BMSCs) were seeded into gelatin sponge and chondrogenically cultured for 4 weeks in vitro to form cartilage templates. The constructs were then implanted subcutaneously in monocyte-depleted mice or normal C57BL/6 mice. Implants harvested at two months showed inferior osteogenic quality in monocyte-depleted mice compared with that of normal mice. In normal mice, the cartilage templates recruited a high ratio of alternatively activated macrophages (CAM or M2) to classically activated macrophages (AAM or M1), compared with empty sponge. In vitro co-culture assay of macrophages with cartilage templates also showed that the cartilage templates polarized macrophages to the M2 phenotype and that these effects were even stronger than those of primary BMSCs. In turn, the co-culture of polarized macrophages with cartilage templates showed that compared to M0 or M2, M1 significantly increased the expressions of osteogenic and angiogenic markers of cartilage templates. These data suggested that macrophages seem to be indispensable in the osteogenesis of cartilage templates and that cartilage templates have a favorable immunomodulatory ability to polarize macrophages to the M2 phenotype. M1 was the contributing phenotype of macrophages that promoted the osteogenesis and angiogenesis of cartilage templates. Macrophages and cartilage templates cooperate to achieve endochondral bone formation.
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