School of Nursing, Jilin University, Changchun 130021, China.
Biomater Sci. 2017 Aug 22;5(9):1820-1827. doi: 10.1039/c7bm00358g.
Mesenchymal stem cells (MSCs) hold great potential for tissue engineering and regeneration medicine. However, for clinical use, MSCs may be detrimental due to their uncertain fate during the transplantation. It is therefore highly desirable to develop biocompatible nanomaterials to integrate cell fate regulation with monitoring for MSC-based therapy. Herein, we employ recently developed citric acid-based carbon dots (CDs) and their derivatives (Et-IPCA) for labeling and tracking of rat bone marrow mesenchymal stem cells (rBMSCs). We further investigate their biocompatibility and effects on the osteogenic differentiation of rBMSCs. These highly fluorescent probes provide labeling of rBMSCs by internalization without affecting cell viability or inducing apoptosis when the concentration is lower than 50 μg mL. Importantly, the presence of the CDs and Et-IPCA facilitates high-efficiency osteogenic differentiation of rBMSCs by promoting osteogenic transcription and enhancing matrix mineralization. Compared to Et-IPCA, CDs considerably provide long-term tracking and promote the differentiation of rBMSCs toward osteoblasts through the ROS-mediated MAPK pathway. Taken together, our results consistently demonstrate that carbon dots are capable of both tracking and enhancing the osteogenic differentiation of MSCs. This study sheds new light on the potential of carbon dots as a bifunctional tool in the thriving field of MSC-based therapy.
间充质干细胞 (MSCs) 在组织工程和再生医学中具有巨大的潜力。然而,对于临床应用,由于在移植过程中其命运不确定,MSCs 可能有害。因此,开发具有生物相容性的纳米材料将细胞命运调控与基于 MSC 的治疗的监测相结合是非常理想的。在此,我们使用最近开发的基于柠檬酸的碳点 (CDs) 及其衍生物 (Et-IPCA) 对大鼠骨髓间充质干细胞 (rBMSCs) 进行标记和跟踪。我们进一步研究了它们的生物相容性及其对 rBMSCs 成骨分化的影响。这些高荧光探针通过内化对 rBMSCs 进行标记,而当浓度低于 50μg/mL 时,不会影响细胞活力或诱导细胞凋亡。重要的是,CDs 和 Et-IPCA 的存在通过促进成骨转录和增强基质矿化促进 rBMSCs 的高效成骨分化。与 Et-IPCA 相比,CDs 通过 ROS 介导的 MAPK 途径极大地提供了 rBMSCs 的长期跟踪,并促进其向成骨细胞分化。总之,我们的研究结果一致表明,碳点能够对 MSCs 的跟踪和增强成骨分化都具有作用。这项研究为碳点作为基于 MSC 治疗这一蓬勃发展领域的多功能工具提供了新的思路。