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Mechanochemical manipulation of hepatocyte aggregation can selectively induce or repress liver-specific function
E J Semler1, C S Ranucci, P V Moghe
1Department of Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, New Jersey 08854, USA.
Biotechnology and Bioengineering
|June 22, 2000
Summary
Growth factors like epidermal growth factor (EGF) and hepatocyte growth factor (HGF) promote liver cell aggregation and function. Their effects depend on the mechanical properties of the culture substrate, influencing liver tissue engineering.
Area of Science:
- Hepatocyte biology and tissue engineering
- Biomaterials science and mechanical properties
- Cellular morphogenesis and differentiation
Background:
- Controlled hepatocyte aggregation is crucial for liver regeneration and tissue reconstruction.
- Hepatotrophic growth factors, including EGF and HGF, influence hepatocyte behavior.
- The mechanical properties of the extracellular matrix microenvironment significantly impact cell function.
Purpose of the Study:
- To quantify the effects of EGF and HGF on hepatocyte aggregation kinetics and liver-specific function.
- To investigate how substrate mechanical compliance influences growth factor-mediated hepatocyte morphogenesis and function.
- To explore the synergistic effects of combined EGF and HGF stimulation on hepatocyte behavior.
Main Methods:
- Culturing hepatocytes on organotypic substrates (Matrigel) with varying mechanical compliance (34 Pa vs. 118 Pa).
- Stimulating hepatocytes with epidermal growth factor (EGF) and hepatocyte growth factor (HGF), individually and in combination.
- Quantifying aggregation kinetics, morphology (2D corded vs. 3D spheroidal), and liver-specific function (albumin secretion rate).
Main Results:
- Growth factor stimulation selectively enhanced aggregation kinetics, forming 2D cords on compliant substrates and 3D spheroids on stiffer substrates.
- Co-stimulation with EGF and HGF synergistically maximized aggregation kinetics in a substrate-dependent manner.
- Substrate mechanical compliance critically modulated growth factor effects on hepatocyte function; high compliance enhanced albumin secretion, while low compliance repressed it.
Conclusions:
- Physicochemical parameters of the culture microenvironment, specifically substrate mechanics and growth factor signaling, interplay to control hepatocyte morphogenesis.
- This interplay can selectively enhance or repress differentiated hepatocyte functions, offering insights for liver tissue engineering strategies.
- Optimizing substrate properties alongside growth factor stimulation is key to achieving desired outcomes in liver cell-based therapies.