CT/NIRF dual-modal imaging tracking and therapeutic efficacy of transplanted mesenchymal stem cells labeled with Au nanoparticles in silica-induced pulmonary fibrosis
CT/NIRF dual-modal imaging tracking and therapeutic efficacy of transplanted mesenchymal stem cells labeled with Au nanoparticles in silica-induced pulmonary fibrosis
复制标题
CT/NIRF双模态成像跟踪及金纳米颗粒标记的移植间充质干细胞对二氧化硅诱导的肺纤维化的治疗效果
DOI：
10.1039/c9tb02652e
复制
发表时间：
2020-02-28
影响因子：
7
通讯作者：
Chao, Jie
中科院分区：
文献类型：
--
作者：
Huang, Jie;Huang, Jie;Chao, Jie
间充质干细胞(MSCs)在细胞治疗和再生医学中显示出良好的治疗效果。临床迫切需要对MSCs进行有效的跟踪，这将有助于我们了解移植后的行为，并允许调整治疗策略。然而，目前还没有临床批准的示踪剂，这限制了干细胞疗法的临床翻译。本研究开发了一种用于CT/荧光双模成像的纳米粒子Au@Alb@ICG@PLL(AA@ICG@PLL)，用于示踪经气管内注射于二氧化硅诱导的肺纤维化小鼠的骨髓间充质干细胞(BMSCs)，这有助于了解干细胞治疗的疗效和可能的分子机制。首先在牛血清白蛋白(BSA)溶液中形成AuNPs，然后用吲哚青绿(ICG)修饰，然后包覆一层多L赖氨酸(PLL)以提高细胞内摄取和生物相容性。用AA@ICG@PLL纳米粒高效标记骨髓间充质干细胞，不影响细胞的生物学功能和治疗能力。移植后注射的AA@ICG@PLL标记的BMSCs可通过CT和近红外荧光(NIRF)成像进行追踪，最长可达21d。利用这些纳米粒子揭示了移植的BMSCs的分子抗炎机制，包括下调促炎细胞因子，抑制巨噬细胞活化，延缓纤维化进程。这项研究表明，基于影像引导的MSC治疗肺纤维化，如特发性肺纤维化(IPF)和尘肺，具有很好的应用前景。
Mesenchymal stem cells (MSCs) have shown promising therapeutic effects in cell-based therapies and regenerative medicine. Efficient tracking of MSCs is an urgent clinical need that will help us to understand their behavior after transplantation and allow adjustment of therapeutic strategies. However, no clinically approved tracers are currently available, which limits the clinical translation of stem cell therapy. In this study, a nanoparticle (NP) for computed tomography (CT)/fluorescence dual-modal imaging, Au@Albumin@ICG@PLL (AA@ICG@PLL), was developed to track bone marrow-derived mesenchymal stem cells (BMSCs) that were administered intratracheally into mice with silica-induced pulmonary fibrosis, which facilitated understanding of the therapeutic effect and the possible molecular mechanism of stem cell therapy. The AuNPs were first formed in bovine serum albumin (BSA) solution and modified with indocyanine green (ICG), and subsequently coated with a poly-l-lysine (PLL) layer to enhance intracellular uptake and biocompatibility. BMSCs were labeled with AA@ICG@PLL NPs with high efficiency without an effect on biological function or therapeutic capacity. The injected AA@ICG@PLL-labeled BMSCs could be tracked via CT and near-infrared fluorescence (NIRF) imaging for up to 21 days after transplantation. Using these NPs, the molecular anti-inflammatory mechanism of transplanted BMSCs was revealed, which included the downregulation of proinflammatory cytokines, suppression of macrophage activation, and delay of the fibrosis process. This study suggests a promising role for imaging-guided MSC-based therapy for pulmonary fibrosis, such as idiopathic pulmonary fibrosis (IPF) and pneumoconiosis.