3.5. Transport of exosomes across the gut epithelium to the BBB
Exosomes are known to move across gut epithelium or BBB (Carobolante, Mantaj, Ferrari, & Vllasaliu, 2020; Saeedi, Israel, Nagy, & Turecki, 2019), and several animal studies imply they play important roles in affecting the cognitive ability (Manca et al., 2018; Mutai, Zhou, & Zempleni, 2017; Zempleni, Sukreet, Zhou, Wu, & Mutai, 2019). Furthermore, exosomes in the blood stream showed natural brain targeting ability (H. Peng et al., 2020). The transport of fluorescence-labeled exosomes across the gut epithelium and BBB was examined in our GBA chip (Fig. 8). In case of the co-culture, uptake of exosomes by the gut layer under flow condition was not significantly affected, while the BBB took up more exosomes under flow condition. However, the presence of flow seemed to induce a slight increase in the exosome uptake by the mono-cultured hBMECs. Taking these results together, it seems that the fluidic condition enhances exosome transport across the gut epithelium, and uptake by the brain endothelial cells. Iason et al. assessed uptake and translocation of angiopoietin-2-modified liposomes in their BBB chip (Papademetriou, Vedula, Charest, & Porter, 2018), and more Ang2-liposomes were transported across the BBB with increasing fluidic shear. Our results also suggest that the fluidic shears stress can affect the exosome translocation across the gut epithelium and brain endothelium.