Expandable Liver Organoids via Defined Medium Composition
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Solution Overview
Problem
Current methods for generating liver organoids from stem cells face challenges in maintaining proliferation activity and functionality, particularly in replicating the characteristics of mature hepatocytes, which are essential for drug efficacy and toxicity testing and disease modeling.
Innovation Solution
A medium composition including basic fibroblast growth factor (bFGF), oncostatin M (OSM), and insulin-transferrin-selenium (ITS) is used to differentiate liver organoids, allowing for up to 90 times subculture and maintaining mature hepatocyte characteristics, enabling effective drug screening and disease modeling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If primary human hepatocytes are used for in vitro liver models, then liver metabolism evaluation accuracy is improved, but proliferation ability and organ functionality are lost
Solution Approach 1:
The patent changes the culture parameters by using a defined medium composition containing specific growth factors (bFGF, OSM, ITS) and culturing conditions (3D suspension culture, specific oxygen tension) to enable human hepatocytes to maintain both metabolic functionality and proliferation ability simultaneously, resolving the contradiction between accuracy and productivity
2Adaptability or versatility
If liver spheroids are generated from pluripotent stem cells, then stem cell-based in vitro liver models are obtained, but proliferation activity and functionality are difficult to maintain
Solution Approach 1:
The patent optimizes culture parameters including defined medium composition with specific growth factors, 3D suspension culture format, and controlled oxygen tension to enable liver spheroids derived from pluripotent stem cells to maintain both proliferation activity and hepatocyte functionality, resolving the contradiction between adaptability and reliability
3Ease of manufacture
If tissue-derived liver organoids are used, then human tissue accessibility is improved, but differentiation potential is limited
Solution Approach 1:
The patent uses a defined medium composition with specific growth factors and culturing conditions to expand the differentiation potential of tissue-derived liver organoids while maintaining ease of manufacture from human tissues, resolving the contradiction between ease of manufacture and adaptability
Data Source
AI summary
The present invention relates to expandable liver organoids, a medium composition for differentiation thereof, and a method for producing liver organoids using the same, and the liver organoids according to the present invention exhibit the characteristics of more mature hepatocytes than 2D differentiated hepatocytes, can be subcultured up to 90 times or more, and exhibit the expandability for maintaining the characteristics of mature hepatocytes even after multiple subcultures, and thus can be usefully utilized for predicting toxicity, regeneration, and inflammatory response, drug screening, and modeling of diseases such as hepatic steatosis.