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Human Liver Spheroids from Peripheral Blood for Liver Disease Studies
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Microfluidic confinement enhances phenotype and function of hepatocyte spheroids.
Jong Hoon Choi1, Lorena Loarca1, Jose M De Hoyos-Vega1
1Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
American Journal of Physiology. Cell Physiology
|July 23, 2020
Summary
Hepatocyte spheroids cultured in microfluidic devices show enhanced function and stability. Inhibiting TGF-β1 signaling further improves albumin synthesis, offering a promising platform for liver disease modeling and drug testing.
Area of Science:
- Hepatocyte cell culture and liver tissue engineering.
- Microfluidics for biological applications.
- Liver disease modeling and regenerative medicine.
Background:
- Primary hepatocytes are crucial for liver research but challenging to maintain.
- Three-dimensional (3-D) hepatocyte spheroids extend cell phenotype.
- Microfluidic devices enhance two-dimensional (2-D) hepatocyte function via growth factors like hepatocyte growth factor (HGF).
Purpose of the Study:
- To investigate if 3-D hepatocyte spheroids cultured in microfluidic devices exhibit enhanced phenotype and function.
- To assess the impact of microfluidic device volume on spheroid function.
- To evaluate the potential of this platform for liver disease modeling and therapeutic testing.
Main Methods:
- Fabrication of microfluidic devices with pyramidal wells to promote spheroid formation (~100 µm diameter).
- Culture of hepatocyte spheroids in small and large volume microfluidic devices.
- Assessment of spheroid function via albumin synthesis, bile acid production, and hepatic enzyme expression.
- Inhibition of transforming growth factor-beta 1 (TGF-β1) signaling to assess long-term function.
- Induction of alcohol injury in microfluidic cultures to test protective effects of interleukin-22.
Main Results:
- Hepatocyte spheroids in low-volume microfluidic devices demonstrated significantly higher functionality compared to those in large-volume devices.
- Enhanced functionality correlated with increased hepatocyte growth factor (HGF) secretion.
- Inhibition of TGF-β1 signaling prevented the typical decay of albumin secretion, maintaining high function for 4 weeks.
- Microfluidic cultures successfully modeled alcohol-induced liver injury and showed potential protective effects of interleukin-22.
Conclusions:
- Microfluidic culture of hepatocyte spheroids significantly enhances liver-specific functions and extends culture stability.
- TGF-β1 signaling inhibition is a key factor in maintaining long-term hepatocyte function in these microfluidic systems.
- This microfluidic spheroid platform is a valuable tool for studying liver diseases and evaluating potential therapies like interleukin-22.
