The complexity behind the 3D cell cultures: the 3D liver cell culture case

Introduction to 3D Liver Cell Culture

Once it is clear how to deal with 3D cell cultures it is time to focus on one type of cells and analyze its strengths and its limitations. In this case, liver cells will be analyzed.

There are some research groups trying to create liver-on-chip but they do not yet approach to a complete solution in terms of cell type diversity and complexity. [1-2] In order to better understand why it is necessary to get aware of the complexity of working with liver cells.

First, it is mandatory to know how the liver works and why it has very complex structure. As it can be seen in Figure 1, there are different types of cells such as hepatocyte, endothelial cells, Kupffer cells or stellate cells. Even if hepatocytes are the main type of liver cell (in terms of number), it will be an error to forget the other types when creating a liver on a chip.

It is important to take care of the specific needs and functions of each of those cells and to know how they interact with each other because a more complex culture cell system can be recreated. Although, the hepatocytes required a very specific 3D structure to be able to keep their liver functions. This needs to be accomplished before any device is done because being able to have a liver functional unit is the key for long-term tests.

Figure 1: Scheme of the different cell types that are present inside the liver Figure 1: Scheme of the different cell types that are present inside the liver

CherryTemp thermal stage

 The World Fastest
temperature controller for live cell imaging


The full content has moved to our new website. Get full access by following the link below.


  1. Toh Y-C, Lim TC, Tai D, Xiao G, van Noort D, Yu H. A microfluidic 3D hepatocyte chip for drug toxicity testing. Lab Chip [Internet]. 2009;9(14):2026.
  2. An Introduction to 3D Cell Culture Tools and Techniques. White Pap. 2012;(Figure 1):1–11.
  3. Mk B, Wang N, Lau W, Liu Q. Dynamic Culture Using Novel Slow Perfusion Biroeactor and Porous Polycaprolactone ( PCL ) Scaffolds for Bone Regeneration and Repair. Technology. :8902.
  4. 3D Biotek Bioreactor System – 3D Bioreactors | Sigma-Aldrich
  5. Fey SJ, Wrzesinski K. Determination of drug toxicity using 3D spheroids constructed from an immortal human hepatocyte cell line. Toxicol Sci [Internet]. 2012;127(2):403–11.
  6. Ramaiahgari SC, den Braver MW, Herpers B, Terpstra V, Commandeur JNM, van de Water B, et al. A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies. Arch Toxicol [Internet]. 2014;88(5):1083–95.
  7. Khetani SR, Bhatia SN. Microscale culture of human liver cells for drug development. Nat Biotechnol
  8. Yip D, Cho CH. A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing. Vol. 433, Biochemical and Biophysical Research Communications. 2013.
  9. Frevert U, Engelmann S, Zougbédé S, Stange J, Ng B, Matuschewski K, et al. Intravital Observation of Plasmodium berghei Sporozoite Infection of the Liver. Egwang T, editor. PLoS Biol. 2005 May;3(6):e192.
  10. Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol

See also :

2D Versus 3D Cell Cultures from Mimetas

3D Cell Culture: A Review of Current Techniques whitepaper from Biotek

3D Cell Culture Tools and Applications From Merk

Written by Pablo Salaverria


Pablo is part of the H2020-MSCA-ITN-ETN-DivIDe European network. LEARN MORE.

CherryTemp thermal stage

Discover the CherryTemp Heater Cooler

Ultra-fast shifts and temperature accuracy at the sample level