Large-scale high-density culture of hepatocytes in a liver microsystem with mimicked sinusoid blood flow
| Autor: | Jing Liu, Weiping Ding, Shengnan Ya, Cheng Shaohui, Dayong Gao, Chengpan Li |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Countercurrent exchange Biomedical Engineering Cell Culture Techniques Medicine (miscellaneous) 02 engineering and technology Biomaterials 03 medical and health sciences 3D cell culture Sinusoid Biomimetics Extracellular Humans Tissue Engineering Chemistry Metabolism Blood flow Hep G2 Cells 021001 nanoscience & nanotechnology Liver Artificial 030104 developmental biology Liver Cell culture Biophysics Hepatocytes Limiting oxygen concentration 0210 nano-technology Blood Flow Velocity |
| Zdroj: | Journal of tissue engineering and regenerative medicine. 12(12) |
| ISSN: | 1932-7005 |
| Popis: | In vitro engineering of liver tissue is a rapidly developing field for various biomedical applications. However, liver tissue culture is currently performed on only a small scale with a low density of hepatocytes. In this study, a simple design was introduced in a liver microsystem to enhance the transport of nutrients (e.g., oxygen and glucose) for the three-dimensional large-scale, high-density culture of hepatocytes. In this design, convection across the cell culture zone was generated to mimic sinusoid blood flow (SBF) based on the pressure difference between two fluids flowing in a countercurrent manner on either side of the cell culture zone. First, the distributions of living and dead cells in different culture subzones under various perfusion flow rates were observed, analysed, and compared. Then, the enhanced transport of nutrients was experimentally validated in relation to the viability of cells and theoretically explained by comparing the fluid velocity and oxygen concentration distribution in the cell culture zone in counterflow and coflow modes. Finally, the functions of the SBF-mimicked liver microsystem were assessed on the basis of specific metabolites, synthesized proteins, and bilirubin detoxification of hepatocytes, with collagen and alginate as extracellular matrices. Under this design, the density of hepatocytes cultured at the 3-mm-thickness scale reached ~7 × 107 cells/ml on Day 7, and the metabolism and detoxification functions of the cells worked well. In addition, a liver rope-like structure and sphere-like clusters of cells were observed. This work provides insight for the design of a bionic liver microsystem. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|