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

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.

Integrating biological vasculature into a multi-organ-chip microsystem

“…The same solution for media recirculation has been used in the multi-channel 3D-micro fluid cell culture system (mFCCS) of Zhang and coworkers to combine individual human liver, lung, kidney, and adipose cell culture compartments. 11 By contrast, the total micro bioassay system of Imura and co-workers, in its most advanced version, constitutively combines human intestine, liver and breast cancer cell cultures in a single linear channel applying unidirectional flow without media recirculation. 12 The establishment of a functional on-chip organ equivalent also requires a significant period of time -e.g.…”

Chip-based liver equivalents for toxicity testing – organotypicalness versus cost-efficient high throughput

“…It is not obvious if specific zonation characteristics can be stably achieved within the system. 63 The formation of 3D tissue-like structures composed of polarised cells which form extended bile canalicular structures was presented by Goral and colleagues (Fig. 2e).…”

“…A thin layer of matrix was layered over the 3D cells by a polyelectrolyte complex coacervation process. 63 The cells preserved their 3D cyto-architecture and cell-specific functions for the whole cultivation period of up to one week. The use of intercellular polymeric linkers, such as polyethyleneimine-hydrazide, which stabilise the multicellular aggregates, facilitate the establishment of a more natural extracellular matrix environment.…”

Exploitation of physical and chemical constraints for three-dimensional microtissue construction in microfluidics

“…We have combined the front-and side-trapping mechanisms into a microfluidic channel with dimensions of 10 4 m ͑length͒ ϫ 600 m ͑width͒ ϫ 100 m ͑height͒, in arrays of micropillars ͑dimensions 30 ϫ 50 m and a 20 m gap size͒ located in the center of the microfluidic channel to filter and trap the cells using a withdrawal flow. 31,[42][43][44][45] These trapped cells maintain good viability, 3D morphology, sufficient cell-cell and cell-matrix interactions, as well as high levels of albumin secretion and UDP-glucuronyltransferase ͑UGT͒ activity for in vitro toxicology applications.…”