Uribe Johana, Liu Han-Yuan, Mohamed Zeinab, Chiou Aaron E, Fischbach Claudia, Daniel Susan
Meinig School of Biomedical Engineering, Cornell University, 101 Weill Hall, 273 Tower Road, Ithaca, New York 14853, United States.
School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, 6-44 Ho Plaza, Ithaca, New York 14853, United States.
ACS Biomater Sci Eng. 2020 Jul 13;6(7):3945-3956. doi: 10.1021/acsbiomaterials.0c00133. Epub 2020 Jun 3.
Extracellular vesicles (EVs) are membrane-encapsulated particles secreted by eukaryotic cells that stimulate cell communication and horizontal cargo exchange. EV interactions with stromal cells can result in molecular changes in the recipient cell and, in some cases, lead to disease progression. However, mechanisms leading to these changes are poorly understood. A few model systems are available for studying the outcomes of surface interactions between EV membranes with stromal cells. Here, we created a hybrid supported bilayer incorporating EVs membrane material, called an extracellular vesicle supported bilayer, EVSB. Using EVSBs, we investigated the surface interactions between breast cancer EVs and adipose-derived stem cells (ADSCs) by culturing ADSCs on EVSBs and analyzing cell adhesion, spreading, viability, vascular endothelial growth factor (VEGF) secretion, and myofibroblast differentiation. Results show that cell viability, adhesion, spreading, and proangiogenic activity were enhanced, conditions that promote oncogenic activity, but cell differentiation was not. This model system could be used to develop therapeutic strategies to limit EV-ADSC interactions and proangiogenic conditions. Finally, this model system is not limited to the study of cancer but can be used to study surface interactions between EVs from any origin and any target cell to investigate EV mechanisms leading to cellular changes in other diseases.
细胞外囊泡（EVs）是真核细胞分泌的膜包裹颗粒，可刺激细胞通讯和水平货物交换。EVs与基质细胞的相互作用可导致受体细胞发生分子变化，在某些情况下，还会导致疾病进展。然而，导致这些变化的机制尚不清楚。有一些模型系统可用于研究EV膜与基质细胞之间表面相互作用的结果。在这里，我们创建了一种包含EV膜材料的混合支持双层膜，称为细胞外囊泡支持双层膜（EVSB）。使用EVSB，我们通过在EVSB上培养脂肪来源干细胞（ADSCs）并分析细胞粘附、铺展、活力、血管内皮生长因子（VEGF）分泌和成肌纤维细胞分化，研究了乳腺癌EVs与ADSCs之间的表面相互作用。结果表明，细胞活力、粘附、铺展和促血管生成活性增强，这些条件促进致癌活性，但细胞分化未增强。该模型系统可用于开发限制EV-ADSC相互作用和促血管生成条件的治疗策略。最后，该模型系统不仅限于癌症研究，还可用于研究任何来源的EVs与任何靶细胞之间的表面相互作用，以研究导致其他疾病细胞变化的EV机制。
