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Hollow Fiber Bioreactors for In Vivo-like Mammalian Tissue Culture
Published on: May 26, 2016
A vertical-flow bioreactor array compacts hepatocytes for enhanced polarity and functions.
Liang Zhu1, Huanming Xia2, Zhenfeng Wang3
1Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore. hanry_yu@nuhs.edu.sg and Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, 638075 Singapore and Institute of Biotechnology and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
This study introduces a novel bioreactor that applies pressure to cultured hepatocytes, mimicking in vivo conditions. This method enhances cell function and morphology for improved drug screening and liver research.
Area of Science:
- Hepatocyte biology
- Bioreactor engineering
- In vitro modeling
Background:
- Hepatocytes in vivo are exposed to intra-abdominal pressure (IAP), a factor typically absent in standard cell culture.
- Cuboidal cell shape and intercellular contact are crucial for maintaining the differentiated hepatic phenotype in vitro.
- Previous microfluidic studies showed pressure application accelerates hepatocyte repolarization and cell-cell interactions.
Purpose of the Study:
- To develop a high-throughput culture platform that incorporates physiological pressure for hepatocytes.
- To design a vertical-flow compaction bioreactor array (VCBA) for mimicking in vivo IAP and portal pressure.
- To assess the impact of pressure-induced compaction on hepatocyte morphology, function, and repolarization.
Main Methods:
- Designed and utilized a vertical-flow compaction bioreactor array (VCBA) for multi-well hepatocyte culture.
- Applied vertical perfusion forces to compact hepatocytes, simulating in vivo pressure ranges.
- Compared hepatocyte culture under pressure-induced compaction versus static conditions.
Main Results:
- Hepatocytes cultured in the VCBA exhibited accelerated repolarization and adopted an in vivo-like cuboidal morphology.
- The bioreactor platform maintained superior hepatocyte functions during long-term culture compared to static cultures.
- Vertical perfusion forces effectively modulated cell compaction and intercellular interactions.
Conclusions:
- The VCBA is a novel engineering tool for controlling hepatocyte compaction and cell-cell interactions.
- This platform offers a promising approach for precise control over hepatocyte repolarization in vitro.
- The findings support the use of pressure-based bioreactors for advanced drug screening and liver research models.
