Mathematical and Experimental Model of Oxygen Diffusion for HepaRG Cell Spheroids

Bull Exp Biol Med. 2016 Apr;160(6):857-60. doi: 10.1007/s10517-016-3326-1. Epub 2016 May 10.


3D cell cultures are extensively used to study in vitro toxic effect of xenobiotics. When using multicellular spheroids, the question about their optimal size should be solved: small spheroids are difficult to manipulate, while large size of spheroids impairs the transport of nutrients and oxygen into the center. Mathematical models describing the distribution of substances in multicellular spheroids numerical procedure for solving differential equation system, which complicates their use in laboratory practice. We proposed and experimentally evaluated a new mathematical model describing oxygen distribution in HepaRG cell spheroids. Markers of functional activity were studied in spheroids of different size. The maximum size of spheroids that can be maintained in culture for 9 days without necrosis was determined.

Keywords: 3D model of the liver; HepaRG; hypoxia; mathematical model.

MeSH terms

  • Cell Line
  • Diffusion
  • Hepatocytes / metabolism
  • Humans
  • Models, Biological
  • Oxygen / metabolism*
  • Oxygen Consumption
  • Spheroids, Cellular / metabolism*


  • Oxygen