Microvascularized tumor organoids-on-chips: advancing preclinical drug screening with pathophysiological relevance

摘要

Microvasculature-on-a-chip technology. a Microfluidic platform to reconstruct a self-organized microvascular network. Configurations and confocal microscopy images presenting the microvasculature constructed by (i) vasculogenesis (scale bar: 100 μm) and (ii) angiogenesis (scale bar: 20 μm) at day 4. [62]. b Self-assembled BBB microvascular network. Schematic diagram of BBB-on-a-chip consisting of endothelial cells, astrocytes (ACs), and neurons (top). Confocal microscopy images of astrocytes (GFAP, white), neurons (Synaptophysin, green), and microvasculature (CD31, red) (bottom-left). Immunostaining of CD31 (red) and tight junctions, ZO-1 (green) of the vascular network—astrocyte interface (bottom-right). [63]. c Microfluidic device to culture endothelial barriers. Configurations of blood-lymphatic endothelial cells layer culture (top). Immunostaining of an endothelial-specific protein, claudin-5, and an endothelial-specific adhesion molecule, VE-cadherin (bottom). Scale bar, 100 μm. [64]. d BBB structure emulated by the microfluidic culture of endothelial cells monolayer. Schematic representation of the microfluidic BBB model (top). (i) Confocal image of the bottom of the chip with endothelium (ZO-1, red) and network of astrocytes (GFAP, white). Scale bar, 50 µm. (ii) Tight endothelial monolayer (ZO-1, red; DAPI, blue), pericytes cultured under the porous membrane (α-SMA, green; DAPI, blue), and astrocytes labeled with GFAP (GFAP, white) and S100β (S100β, magenta). Scale bar, 50 μm [65]. e Tubular endothelial barrier-on-a-chip. Schematic representation of the microfluidic system(top). Confocal microscopy images of the overall endothelialized ductal structure and the magnified section of network corner (red, CD31; blue, nuclei) (bottom). Scale bar, 100 μm [66]. f Ductal structure of BBB reproduced by microfluidic technology. Cross-section view of the center of the chip for a three-lane coculture system of endothelial cells, pericytes, and astrocytes (top). (i) Z-stack confocal image of 3D reconstructed BBB (Calcein-AM, green and magenta; PECAM-1, red; nuclei, blue). (ii) Images of FITC-dextran (20 kDa) perfused in the microchannels [67]