Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, Jiangsu 215123, China.
J Mater Chem B. 2020 Feb 26;8(8):1713-1727. doi: 10.1039/c9tb02652e.
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.
间充质干细胞（MSCs）在细胞治疗和再生医学中显示出有前景的治疗效果。高效追踪 MSCs 是一种迫切的临床需求，它将帮助我们了解它们在移植后的行为，并允许调整治疗策略。然而，目前没有临床批准的示踪剂，这限制了干细胞治疗的临床转化。在这项研究中，开发了一种用于计算机断层扫描（CT）/荧光双模式成像的纳米颗粒（NP），Au@Albumin@ICG@PLL（AA@ICG@PLL），用于追踪骨髓间充质干细胞（BMSCs），这些细胞通过气管内给药到二氧化硅诱导的肺纤维化小鼠中，这有助于了解干细胞治疗的治疗效果和可能的分子机制。首先在牛血清白蛋白（BSA）溶液中形成 AuNPs，并对其进行吲哚菁绿（ICG）修饰，随后用聚-l-赖氨酸（PLL）层进行涂层，以增强细胞内摄取和生物相容性。AA@ICG@PLL NPs 以高效率标记 BMSCs，而对其生物学功能或治疗能力没有影响。注入的 AA@ICG@PLL 标记的 BMSCs 可以通过 CT 和近红外荧光（NIRF）成像进行追踪，最长可达移植后 21 天。使用这些 NPs，揭示了移植 BMSCs 的分子抗炎机制，包括下调促炎细胞因子、抑制巨噬细胞激活和延缓纤维化过程。这项研究表明，成像引导的 MSC 为基础的治疗方法对肺纤维化（如特发性肺纤维化（IPF）和尘肺）具有很大的应用前景。
