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Mathematical modelling of oxygen gradients in stem cell-derived liver tissue
- Source :
- PLoS ONE, PLOS ONE, Leedale, J, Lucendo-Villarin, B, Meseguer Ripolles, J, Kasarinaite, A, Webb, S D & Hay, D C 2021, ' Mathematical modelling of oxygen gradients in stem cell-derived liver tissue ', PLoS ONE, vol. 16, no. 2, e0244070 . https://doi.org/10.1371/journal.pone.0244070, PLoS ONE, Vol 16, Iss 2, p e0244070 (2021)
- Publication Year :
- 2020
-
Abstract
- A major bottleneck in the study of human liver physiology is the provision of stable liver tissue in sufficient quantity. As a result, current approaches to modelling human drug efficacy and toxicity rely heavily on immortalized human and animal cell lines. These models are informative but do possess significant drawbacks. To address the issues presented by those models, researchers have turned to pluripotent stem cells (PSCs). PSCs can be generated from defined genetic backgrounds, are scalable, and capable of differentiation to all the cell types found in the human body, representing an attractive source of somatic cells for in vitro and in vivo endeavours. Although unlimited numbers of somatic cell types can be generated in vitro, their maturation still remains problematic. In order to develop high fidelity PSC-derived liver tissue, it is necessary to better understand the cell microenvironment in vitro including key elements of liver physiology. In vivo a major driver of zonated liver function is the oxygen gradient that exists from periportal to pericentral regions. In this paper, we demonstrate how cell culture conditions for PSC-derived liver sphere systems can be optimised to recapitulate physiologically relevant oxygen gradients by using mathematical modelling. The mathematical model incorporates some often-understated features and mechanisms of traditional spheroid systems such as cell-specific oxygen uptake, media volume, spheroid size, and well dimensions that can lead to a spatially heterogeneous distribution of oxygen. This mathematical modelling approach allows for the calibration and identification of culture conditions required to generate physiologically realistic function within the microtissue through recapitulation of the in vivo microenvironment.
- Subjects :
- 0301 basic medicine
Pulmonology
Somatic cell
Cellular differentiation
02 engineering and technology
Mathematical and Statistical Techniques
Animal Cells
Medicine and Health Sciences
Induced pluripotent stem cell
Multidisciplinary
Simulation and Modeling
Cell Differentiation
021001 nanoscience & nanotechnology
Cell biology
Chemistry
Liver
Physical Sciences
Medicine
Biological Cultures
Stem cell
Cellular Types
Anatomy
0210 nano-technology
Research Article
Chemical Elements
Pluripotent Stem Cells
Cell type
Science
Geometry
Biology
Research and Analysis Methods
03 medical and health sciences
In vivo
Medical Hypoxia
Sine Waves
Humans
Biology and Life Sciences
Cell Biology
Models, Theoretical
Cell Cultures
Oxygen
030104 developmental biology
Radii
Cell culture
Hepatocytes
Liver function
Mathematical Functions
Mathematics
Developmental Biology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 16
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....6467e2b583ea174f591b85d129ab7338
- Full Text :
- https://doi.org/10.1371/journal.pone.0244070