Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts - Sorbonne Université Access content directly
Journal Articles Laboratory Investigation Year : 2016

Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts

Pierre-Yves Boelle
Grégoire Bisch
  • Function : Author
Rolland Delelo
  • Function : Author
François Paye
  • Function : Author
Olivier Scatton
  • Function : Author
Chantal Housset
  • Function : Author
Jérôme Becquart
  • Function : Author
Yvon Calmus
  • Function : Author
Filomena Conti
  • Function : Author

Abstract

We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2'-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0.74±0.03 for cyclosporine A (CsA) and 2.4±0.10 for transforming growth factor-beta (TGF-β) (P<0.0001 vs no treatment) for α-SMA expression. Inter-subject variations in α-SMA and Coll1 expression enabled the classification of subjects as potentially low or high fibrosers. Finally, we observed that pirfenidone (which has beneficial effects in vivo) significantly reduced the expressions of α-SMA and Coll1, whereas the angiotensin-converting enzyme inhibitor losartan (which has no effect in vivo) had no significant effect. Our model may thus detect the antifibrotic properties of drugs. Antifibrotic drugs with promising clinical relevance could possibly be selected using a bank of HLMFs from high fibrosers.

Dates and versions

hal-03978901 , version 1 (08-02-2023)

Identifiers

Cite

Lynda Aoudjehane, Pierre-Yves Boelle, Grégoire Bisch, Rolland Delelo, François Paye, et al.. Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts. Laboratory Investigation, 2016, ⟨10.1038/labinvest.2016.36⟩. ⟨hal-03978901⟩
7 View
0 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More