Human Hepatocyte Density in Alginate Beads via Plasma Media
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Solution Overview
Problem
Current methods for growing cells in a matrix, such as alginate beads, face challenges in achieving high cell densities necessary for scalable bio-artificial liver development, leading to difficulties in nutrient and oxygen supply, and existing bio-artificial liver systems are limited by the need for large volumes and reliance on animal components.
Innovation Solution
Supplementing culture media with leukocyte-depleted fresh frozen plasma instead of foetal calf serum to achieve higher cell densities in alginate beads, using a fluidised bed bioreactor with alginate beads and density modifiers to grow human hepatocyte cell lines to performance competence, resulting in a bio-artificial liver with a significantly reduced volume requirement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If foetal calf serum is used to supplement culture media, then cells can be grown, but cell density remains limited to around 10^6 cells/ml
Solution Approach 1:
The patent changes the chemical composition parameter of the culture media by replacing foetal calf serum with human plasma (specifically leukocyte-depleted fresh frozen plasma). This parameter change fundamentally alters the growth environment, enabling cells to proliferate to densities exceeding 10^7 cells/ml, representing an order of magnitude improvement in cell density that directly addresses the scaling capability limitation.
2Reliability
If cell density is increased to improve liver function, then performance competence improves, but volume of biological component increases
Solution Approach 1:
By changing the culture media composition to human plasma, the patent achieves higher cell density packing within the same volume. This allows the system to maintain or improve liver function performance while reducing the overall volume of the biological component required, as more functional cells are concentrated in each unit volume of the bioreactor.
3Productivity
If animal components (foetal calf serum) are used in culture media, then cell growth is supported, but safety concerns and commercialisation barriers arise
Solution Approach 1:
The patent replaces the animal-derived foetal calf serum with human plasma, specifically leukocyte-depleted fresh frozen plasma. This substitution eliminates the safety concerns associated with animal components while maintaining effective cell proliferation. The use of human plasma creates a more clinically relevant and safer system for potential therapeutic applications.
Data Source
AI summary
The present invention relates to a method of growing a plurality of cells (110) to performance competence in a matrix forming agent (120) containing one or more density modifiers (130), characterized in that the cells are grown in a culture media supplemented with from 2-20% human plasma. It also relates to a biological component (100) comprising: i. a matrix forming agent (120), ii. a plurality of cells (110), and iii. one or more density modifiers (130), wherein at performance competence, the cells are present in the matrix forming agent at a density of at least 3 x107 cells/ml.