Laboratory of Tumor Angiogenesis, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA, USA.
Department of Pediatrics & Human Development, Grand Rapids Research Center, Michigan State University, Grand Rapids, MI, USA.
Nanomedicine. 2019 Oct;21:102072. doi: 10.1016/j.nano.2019.102072. Epub 2019 Aug 1.
Exosomes are critical mediators of intercellular crosstalk and are regulator of the cellular/tumor microenvironment. Exosomes have great prospects for clinical application as a theranostic and prognostic probe. Nevertheless, the advancement of exosomes research has been thwarted by our limited knowledge of the most efficient isolation method and their in vivo trafficking. Here we have shown that a combination of two size-based methods using a 0.20 μm syringe filter and 100 k centrifuge membrane filter followed by ultracentrifugation yields a greater number of uniform exosomes. We also demonstrated the visual representation and quantification of the differential in vivo distribution of radioisotope I-labeled exosomes from diverse cellular origins, e.g., tumor cells with or without treatments, myeloid-derived suppressor cells and endothelial progenitor cells. We also determined that the distribution was dependent on the exosomal protein/cytokine contents. The applied in vivo imaging modalities can be utilized to monitor disease progression, metastasis, and exosome-based targeted therapy.
外泌体是细胞间通讯的关键介质，也是细胞/肿瘤微环境的调节因子。外泌体作为治疗和预后探针具有广阔的临床应用前景。然而，由于我们对外泌体最有效的分离方法和体内运输方式了解有限，外泌体的研究进展受到了阻碍。在这里，我们展示了一种组合的两种基于大小的方法，使用 0.20μm 注射器过滤器和 100k 离心膜过滤器，然后进行超速离心，可以获得更多均匀的外泌体。我们还证明了放射性同位素 I 标记的来自不同细胞来源的外泌体，如具有或不具有治疗的肿瘤细胞、髓系来源的抑制细胞和内皮祖细胞，在体内的差异分布的可视化表示和定量。我们还确定，这种分布依赖于外泌体的蛋白/细胞因子含量。所应用的体内成像方式可用于监测疾病进展、转移和基于外泌体的靶向治疗。
