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Concave microwell based size-controllable hepatosphere as a three-dimensional liver tissue model
Sau Fung Wong1, Da Yoon No, Yoon Young Choi
1Department of Biomedical Engineering, Korea University, Seoul 136-701, Republic of Korea.
Biomaterials
|August 5, 2011
Summary
Researchers created controllable liver spheroids (hepatospheres and heterospheres) using primary hepatocytes and hepatic stellate cells (HSCs). These heterospheres show improved albumin secretion and cytochrome P450 activity, aiding liver tissue engineering.
Area of Science:
- Biotechnology
- Cell Biology
- Tissue Engineering
Background:
- Liver disease necessitates advanced tissue models for research and therapy.
- Current liver spheroid models face challenges in size control and functional maturation.
Purpose of the Study:
- To develop size-controllable hepatosphere and heterosphere models.
- To investigate the role of hepatic stellate cells (HSCs) in spheroid formation and function.
- To assess the metabolic capabilities of the developed liver spheroids.
Main Methods:
- Mono-culturing of primary hepatocytes to form hepatospheres.
- Co-culturing primary hepatocytes with HSCs in concave microwell arrays to form heterospheres.
- Quantitative and qualitative analysis of spheroid formation and cell-cell contact.
- Metabolic function assays including albumin and urea secretion.
- Cytochrome P450 enzymatic activity assays.
Main Results:
- Uniform-sized heterospheres rapidly and homogeneously self-aggregated in microwell arrays.
- HSCs significantly influenced spheroid organization and cell-cell contact formation.
- Heterospheres exhibited 30% higher albumin secretion than hepatospheres by day 8.
- Heterospheres showed comparable urea secretion to hepatospheres.
- Enzymatic activity of cytochrome P450 was higher in heterospheres after 9 days of culture.
Conclusions:
- Size-controllable heterospheres can be mass-produced using concave plates.
- HSCs are crucial for organizing hepatocyte aggregates and enhancing spheroid function.
- These heterospheres represent a promising model for artificial hepatic tissue constructs and liver regeneration.
