Rat multicellular 3D liver microtissues to explore TGF-β1 induced effects
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Publication date
13.11.2019
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01A - Journal article
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Journal of Pharmacological and Toxicological Methods
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Volume
101
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Elsevier
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Abstract
Chronic liver damage can lead to fibrosis, encompassing hepatocellular injury, activation of Kupffer cells (KC), and activation of hepatic stellate cells (HSC). Inflammation and TGF-β1 are known mediators in the liver fibrosis adverse outcome pathway (AOP). The aim of this project was to develop a suitable rodent cell culture model for the investigation of key events involved in the development of liver fibrosis, specifically the responses to pathophysiological stimuli such as TGF-β1 and LPS-triggered inflammation.
We optimized a single step protocol to purify rat primary hepatocytes (Hep), HSC and KC cells to generate 3D co-cultures based on the hanging drop method.
This primary multicellular model responded to the profibrotic cytokine TGF-β1 (1 ng/mL) with signs of hepatocellular damage, inflammation and ultimately HSC activation (increase in αSMA expression). LPS elicited an inflammatory response characterized by increased expression of cytokines.
3D-monocultures comprising only Hep displayed different responses, underlying that parenchymal and non-parenchymal cells need to be present in the system to recapitulate fibrosis. The data also suggest that pre-activated HSC may reverse to a quiescent phenotype in 3D, probably due to the more physiological conditions.
Keywords
Hepatic stellate cell, Kupffer cell, Microtissues, TGF-β1, Translational
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1873-488X
1056-8719
1056-8719
Language
English
Created during FHNW affiliation
Yes
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Publication status
Published
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Peer review of the complete publication
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Citation
Prestigiacomo, V., Weston, A., & Suter-Dick, L. (2019). Rat multicellular 3D liver microtissues to explore TGF-β1 induced effects. Journal of Pharmacological and Toxicological Methods, 101. https://doi.org/10.1016/j.vascn.2019.106650