Figures
Fig. 1 Schematics of Gut-Brain Axis (GBA). (A) Gut-BBB-Brain
interaction. (B) Gut-Brain communication through blood stream. Created
with BioRender.com.
Fig. 2 The design of GBA chip and the picture of assembled GBA chip (A)
Cross-sectional view of assembled chip. (B) Schematics of of each
module. (C) Image of the assembled chip.
Fig. 3 The scheme of TEER measurement in the chip. (A) Illustrations on
TEER measurement. Comparison of TEER value between static chip-cultured
cells and transwell-cultured cells for (B) gut barrier module and (C)
BBB module. NS: Not significant; p>0.05, Student’s t-test
(n=3).
Fig. 4 COMSOL Multiphysics simulation of fluidic shear stress inside the
GBA chip. Simulation for (A) gut barrier module and (B) BBB module.
Fig. 5 Fluorescent images of cells seeded in the chip. Live/daed Images
of (A) Caco-2, (B) bEnd.3, and (C) hBMECs when co-cultured (green=live,
red=dead). F-actin/nucleus stain images of (D) Caco-2 cells, (E) bEnd.3
cells and (F) hBMECs when co-cultured (blue=nucleus, green=F-actin).
Fig. 6 LPS-induced changes in co-culture chip and mono-culture
transwell. Changes in Caco-2 barrier represented as (A) TEER and (B)
permeability coefficient. Changes in bEnd.3 barrier represented as (C)
TEER and (D) permeability coefficient. Changes in cytokine secretion of
(E) Caco-2-hBMECs co-culture chip, (F) Caco-2 mono-cultured in the well
and (G) hBMECs mono-cultured in the well. NS: Not significant;
p>0.05, **p<0.01, ***p<0.001, Student’s
t-test (n≥3).
Fig. 7 Changes in barrier functions of cells by butyrate in chips and
wells. Changes in TEER value of (A) Caco-2 co-cultured in chip, (B)
hBMECs co-cultured in chip and (C) hBMECs mono-cultured in transwell.
NaB : Sodium butyrate, NS: Not significant; p>0.05,
**p<0.01, ***p<0.001, Student’s t-test (n≥3).
Fig. 8 Exosome delivery to BBB across gut barrier in the co-culture
chip. (A) co-cultured gut epithelium, (B) co-cultured brain endothelium
(C) mono-cultured brain endothelium in the absence of flow
(blue=nucleus, green=exosome). (D) co-cultured gut epithelium, (E)
co-cultured brain endothelium and (F) mono-cultured brain endothelium in
the presence of flow (blue=nucleus, green=exosome). Quantitative
comparison of exosome uptake with presence or absence of flow on (G)
co-cultured gut epithelium, (H) co-cultured brain endothelium and (I)
mono-cultured brain endothelium. NS: Not significant;
p>0.05, *p<0.05, Student’s t-test (n=3)