Xu Hong, Qiu Yuyou, Xiong Zuogang, Shao Wenjun, Zhang Qi, Tang Guangyu
Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yanchang Road, Shanghai 200072, P. R. China; Department of Radiology, Northern Jiangsu People's Hospital, Clinical Medical School of Yangzhou University, No. 98 Nantong West Road, Yangzhou, Jiangsu 225001, P. R. China.
Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yanchang Road, Shanghai 200072, P. R. China.
Mater Sci Eng C Mater Biol Appl. 2021 Mar;122:111842. doi: 10.1016/j.msec.2020.111842. Epub 2021 Jan 6.
Osteoporosis (OP) is a significant public health problem with associated fragility fractures, thereby causing large bone defects and difficulty in self-repair. The introduction of human mesenchymal stem cells (hMSCs) is the most promising platform in bone tissue engineering for OP therapy, which induces less side effects than conventional medication. However, the safety and efficiency of the cell-based OP therapy requires the ability to monitor the cell's outcome and biodistribution after cell transplantation. Therefore, we designed an in vivo system to track hMSCs in real time and simultaneously attempted to obtain a significant therapeutic effect during the bone repair process. In this study, we synthesized Ir(III) complex, followed by encapsulation with biodegradable methoxy-poly(ethylene glycol) poly(lactic-co-glycolic acid) nanospheres through double emulsions strategy. The Ir(III) complex nanospheres did not affect hMSC proliferation, stemness, and differentiation and realized highly efficient and long-term cellular labeling for at least 25 days in vivo. The optimal transplantation conditions were also determined first by injecting a gradient number of labeled hMSCs percutaneously into the cranial defect of the nude mouse model. Next, we applied this method to ovariectomy-induced OP mice. Results showed long-term optical imaging with high fluorescence intensity and computed tomography (CT) scanning with significantly increased bone formation between the osteoporotic and sham-operated bones. During the tracking process, two mice from each group were sacrificed at two representative time points to examine the bony defect bridging via micro-CT morphometric analyses. Our data showed remarkable promise for efficient hMSC tracking and encouraging treatment in bioimaging-guided OP stem cell therapy.
骨质疏松症（OP）是一个严重的公共卫生问题，伴有脆性骨折，从而导致大的骨缺损和自我修复困难。引入人间充质干细胞（hMSCs）是骨组织工程中治疗OP最有前景的平台，其副作用比传统药物少。然而，基于细胞的OP治疗的安全性和有效性需要监测细胞移植后的细胞结局和生物分布。因此，我们设计了一种体内系统来实时追踪hMSCs，并同时试图在骨修复过程中获得显著的治疗效果。在本研究中，我们合成了铱（III）配合物，然后通过双乳液策略用可生物降解的甲氧基聚（乙二醇）聚（乳酸-乙醇酸）纳米球进行包封。铱（III）配合物纳米球不影响hMSC的增殖、干性和分化，并在体内实现了至少25天的高效长期细胞标记。首先通过将梯度数量的标记hMSCs经皮注射到裸鼠模型的颅骨缺损中确定了最佳移植条件。接下来，我们将此方法应用于卵巢切除诱导的OP小鼠。结果显示，在骨质疏松和假手术的骨骼之间，长期光学成像具有高荧光强度，计算机断层扫描（CT）扫描显示骨形成显著增加。在追踪过程中，每组在两个代表性时间点处死两只小鼠，通过显微CT形态计量分析检查骨缺损桥接情况。我们的数据表明，在生物成像引导的OP干细胞治疗中，高效追踪hMSCs和令人鼓舞的治疗效果具有显著前景。
