Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells

Baltasar Lucendo-Villarin, Panagiotis Filis, Madeleine J Swortwood, Marilyn A Huestis, Jose Meseguer-Ripolles, Kate Cameron, John P Iredale, Peter J O’Shaughnesy, Paul A Fowler , David C Hay (Corresponding Author)

Research output: Contribution to journalArticle

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Abstract

The liver is a dynamic organ which is both multifunctional and highly regenerative. A major role of the liver is to process both endo and xenobiotics. Cigarettes are an example of a legal and widely used drug which can cause major health problems for adults and constitute a particular risk to the foetus, if the mother smokes during pregnancy. Cigarette smoke contains a complex mixture of thousands of different xenobiotics, including nicotine and polycyclic aromatic hydrocarbons. These affect foetal development in a sex-specific manner, inducing sex-dependant molecular responses in different organs. To date, the effect of maternal smoking on the foetal liver has been studied in vitro using cell lines, primary tissue and animal models. While these models have proven to be useful, poor cell phenotype, tissue scarcity, batch-to-batch variation and species differences have led to difficulties in data extrapolation toward human development. Therefore, in this study we have employed hepatoblasts, derived from pluripotent stem cells, to model the effects of xenobiotics from cigarette smoke on human hepatocyte development. Highly pure hepatocyte populations (>90%) were produced in vitro and exposed to factors present in cigarette smoke. Analysis of ATP levels revealed that, independent of the sex, the majority of smoking derivatives tested individually did not deplete ATP levels below 50%. However, following exposure to a cocktail of smoking derivatives, ATP production fell below 50% in a sex-dependent manner. This was paralleled by a loss metabolic activity and secretory ability in both female and male hepatocytes. Interestingly, cell depletion was less pronounced in female hepatocytes, whereas caspase activation was ~twofold greater, indicating sex differences in cell death upon exposure to the smoking derivatives tested.
Original languageEnglish
Pages (from-to)3633-3643
Number of pages11
JournalArchives of Toxicology
Volume91
Issue number11
Early online date16 May 2017
DOIs
Publication statusPublished - Nov 2017

Fingerprint

Maternal Exposure
Pluripotent Stem Cells
Stem cells
smoking
Smoke
Tobacco Products
smoke
Hepatocytes
Xenobiotics
xenobiotics
Smoking
stem
Liver
Adenosine Triphosphate
Human Development
Derivatives
modeling
Tissue
Aptitude
Polycyclic Aromatic Hydrocarbons

Keywords

  • maternal smoking
  • human development
  • pluripotent stem cells
  • hepatocytes
  • apoptosis
  • necrosis

ASJC Scopus subject areas

  • Environmental Science(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Lucendo-Villarin, B., Filis, P., Swortwood, M. J., Huestis, M. A., Meseguer-Ripolles, J., Cameron, K., ... Hay, D. C. (2017). Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells. Archives of Toxicology, 91(11), 3633-3643. https://doi.org/10.1007/s00204-017-1983-0

Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells. / Lucendo-Villarin, Baltasar ; Filis, Panagiotis; Swortwood, Madeleine J ; Huestis, Marilyn A; Meseguer-Ripolles, Jose ; Cameron, Kate ; Iredale, John P; O’Shaughnesy, Peter J ; Fowler , Paul A; Hay, David C (Corresponding Author).

In: Archives of Toxicology, Vol. 91, No. 11, 11.2017, p. 3633-3643.

Research output: Contribution to journalArticle

Lucendo-Villarin, B, Filis, P, Swortwood, MJ, Huestis, MA, Meseguer-Ripolles, J, Cameron, K, Iredale, JP, O’Shaughnesy, PJ, Fowler , PA & Hay, DC 2017, 'Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells', Archives of Toxicology, vol. 91, no. 11, pp. 3633-3643. https://doi.org/10.1007/s00204-017-1983-0
Lucendo-Villarin B, Filis P, Swortwood MJ, Huestis MA, Meseguer-Ripolles J, Cameron K et al. Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells. Archives of Toxicology. 2017 Nov;91(11):3633-3643. https://doi.org/10.1007/s00204-017-1983-0
Lucendo-Villarin, Baltasar ; Filis, Panagiotis ; Swortwood, Madeleine J ; Huestis, Marilyn A ; Meseguer-Ripolles, Jose ; Cameron, Kate ; Iredale, John P ; O’Shaughnesy, Peter J ; Fowler , Paul A ; Hay, David C. / Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells. In: Archives of Toxicology. 2017 ; Vol. 91, No. 11. pp. 3633-3643.
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