Towards a human-on-chip: Culturing multiple cell types on a chip with compartmentalized microenvironments

TLDR

The study designs a multi‑channel 3D microfluidic system to culture multiple organ‑specific 3D cell aggregates simultaneously, aiming to mimic the human body for drug screening. The system uses four human cell types (liver C3A, lung A549, kidney HK‑2, adipose HPA) cultured in separate channels, with growth‑factor‑supplemented medium and gelatin‑microsphere‑mediated TGF‑β1 release to create cell‑specific microenvironments. TGF‑β1 selectively enhanced A549 function without affecting C3A, HK‑2, or HPA, demonstrating limited cross‑talk and suggesting the platform could replace animal models in drug screening.

Abstract

We have developed a multi-channel 3D microfluidic cell culture system (multi-channel 3D-microFCCS) with compartmentalized microenvironments for potential application in human drug screening. To this end, the multi-channel 3D-microFCCS was designed for culturing different 3D cellular aggregates simultaneously to mimic multiple organs in the body. Four human cell types (C3A, A549, HK-2 and HPA) were chosen to represent the liver, lung, kidney and the adipose tissue, respectively. Cellular functions were optimized by supplementing the common medium with growth factors. However, TGF-beta1 was found to enhance A549 functions but inhibit C3A functions. Therefore, TGF-beta1 was specifically controlled-released inside the A549 compartment by means of gelatin microspheres mixed with cells, thus creating a cell-specific microenvironment. The function of A549 cells was enhanced while the functions of C3A, HK-2 and HPA cells were uncompromised, demonstrating the limited cross-talk between cell culture compartments similar to the in vivo situation. Such a multi-channel 3D-microFCCS could be potentially used to supplement or even replace animal models in drug screening.