Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Room 701, No. 3 Building, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Stem Cell Res Ther. 2018 Apr 11;9(1):100. doi: 10.1186/s13287-018-0818-0.
With the development of osteoimmunology and bone tissue engineering (BTE), it has been recognized that the immunomodulatory properties of bone biomaterials have considerable impact in determining their fate after implantation. In this regard, the polarization of macrophages secondary to biomaterials is postulated to play a crucial role in modulating their osteogenesis; thus, strategies that may facilitate this process engender increasing levels of attention. Whereas a variety of reports highlight the immunomodulation of bone marrow mesenchymal stem cells (BMSCs) in cell therapy or their osteogenesis in BTE, few have focused on the effect of BMSCs in promoting osteogenesis in BTE through regulating the phenotype of macrophages. Accordingly, there is an urgent need to clarify the immunomodulatory properties of agents such as laponite (Lap), which is comprised of bioactive silicate nanoplatelets with excellent osteogenesis-inducing potential, to enhance their use in BTE.
In the present study, we analyzed the osteoimmunomodulatory properties of Lap alone, as well as following the introduction of BMSCs into Lap, to determine whether BMSCs could modulate its immunomodulatory properties and promote osteogenesis.
It was found that the BMSCs reversed the polarization of murine-derived macrophage RAW 264.7 cells from M1 as induced by pure Lap to M2 and promoted osteogenesis. In vivo study confirmed that BMSCs combined with Lap initiated a less severe immune response and had an improved effect on bone regeneration compared with Lap alone, which corresponded with the in vitro evaluation.
These results suggest that BMSCs could ameliorate the inflammation induced by Lap and enhance its bone formation. The immunomodulatory characteristics of BMSCs suggest that these might be tailored as a new strategy to promote the osteogenic capacity of biomaterials.
随着骨免疫学和骨组织工程（BTE）的发展，人们已经认识到骨生物材料的免疫调节特性对其植入后的命运有很大的影响。在这方面，生物材料引起的巨噬细胞极化被认为在调节其成骨作用方面起着至关重要的作用；因此，促进这一过程的策略引起了越来越多的关注。虽然有许多报道强调了骨髓间充质干细胞（BMSCs）在细胞治疗中的免疫调节作用或在 BTE 中的成骨作用，但很少有研究关注 BMSCs 通过调节巨噬细胞表型来促进 BTE 中的成骨作用。因此，迫切需要阐明诸如拉蓬（Lap）等药物的免疫调节特性，Lap 由具有优异成骨诱导潜力的生物活性硅酸盐纳米片组成，以增强其在 BTE 中的应用。
在本研究中，我们分析了单独的 Lap 以及在将 BMSCs 引入 Lap 后的骨免疫调节特性，以确定 BMSCs 是否可以调节其免疫调节特性并促进成骨作用。
研究发现，BMSCs 将由纯 Lap 诱导的鼠源性巨噬细胞 RAW 264.7 细胞从 M1 极化逆转到 M2，并促进成骨作用。体内研究证实，与单独使用 Lap 相比，BMSCs 与 Lap 结合可引发较轻的免疫反应，并改善骨再生效果，这与体外评估结果一致。
这些结果表明，BMSCs 可以减轻 Lap 引起的炎症并增强其骨形成。BMSCs 的免疫调节特性表明，可以将其作为一种新策略来提高生物材料的成骨能力。
