Fig. 1: The hiPSCs-derived gut-on-a-chip model. | Nature Biomedical Engineering

Fig. 1: The hiPSCs-derived gut-on-a-chip model.

From: A gut-on-a-chip incorporating human faecal samples and peristalsis predicts responses to immune checkpoint inhibitors for melanoma

Fig. 1: The hiPSCs-derived gut-on-a-chip model.

a, The device is composed of an intestinal epithelial channel and a vascular endothelial channel separated by ECM-like gel; a superimposed actuation chamber allows cyclic controlled deformation of the construct that mimics peristalsis. PDMS, polydimethylsiloxane. b, Microfluidic device and external actuation system. c, Brightfield and live/dead fluorescence image of hiPSCs-derived organoids in plate. d, Representative confocal images (n = 13 in 2 independent experiments) of intestinal cells from disaggregated hiPSCs-derived organoids after 9 days of culture on chip. DAPI (blue), ZO-1 (green), Ki67 (cyan) and villin (magenta). e,f, Epithelial cells polarization from disaggregated organoids. Representative confocal image and fluorescence intensity plot on z axis of nuclei (DAPI, blue) and apical occludins (ZO-1, green) in combination either with villin (magenta, e) or MUC5AC (red, f). g, Representative confocal images (n > 4 in 2 independent experiments) of the different intestinal cell lineages from disaggregated hiPSCs-derived organoids after 9 days of culture on chip. MUC5AC (red), MUC2 (yellow), E-cadherin (white), ZO-1 (green), chromogranin A (cyan, Chromo A) and lysozyme (magenta). Chromo A, chromogranin A. h,i, Fluorescence microscopy images (h) and quantification (i) of Ki67 (cyan), villin (magenta), MUC5AC (red) and MUC2 (yellow) in static versus actuated chips. Mechanical actuation resulted in increased proliferation (Ki67, nstatic = 4, nactuated = 4, P = 0.0368), maturation (villin, nstatic = 3, nactuated = 3, P = 0.0035) and mucus production (MUC5AC, nstatic = 2, nactuated = 4; MUC2, nstatic = 1, nactuated = 2). Bars represent mean ± s.d., two-tailed unpaired t-test. *P ≤ 0.05; **P ≤ 0.01. A, area; Stat, static chips; Act, actuated chips. j, Representative brightfield images (n > 8 in 2 independent experiments) of epithelial cells from disaggregated hiPSCs-derived organoids cultured in static versus actuated conditions highlighting the formation of 3D villi-like structures. k, Representative confocal images (n = 13 in 2 independent experiments) and 3D reconstruction of villi-like structure on chip. Dashed lines indicate the axis along with the (x,z) and (z,y) confocal images used for the reconstructions where taken.

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