Loss of organ function due to illness or accidents can be treated by transplantation using a functioning organ from a donor. However, organ transplantation has limitations such as the chronic shortage of organ donors and the risk of transplant rejection. Regenerative medicine using induced pluripotent stem (iPS) cells, from which various types of organ-specific cells and tissues can be derived, is expected to overcome such limitations and risks.
However, there are several problems that must be overcome in deriving organ-specific cells and tissues. Yokogawa is focusing in particular on two technological challenges. The first challenge is that technology has not yet been established for stable large-scale production of target cells from iPS cells, resulting in inconsistent cell quality. The second challenge is that the lack of technology for creating iPS-derived cells and tissues that function as well as the actual cells and organs in the body. Yokogawa is working to develop in-line quality control technology and cell culture technology to obtain highly functional tissues, in order to contribute to stable production of functional cells and tissues.
We aim to solve problems in cell manufacturing based on non-invasive imaging technology that has little effect on cells.
1.Imaging-based cell evaluation technology
Manual microscopic observation and imaging of cells, which have little effect on cells, are standard methods used for the evaluation of cells during cell culture. In support of advanced life science research, Yokogawa provides a system that can collect more information from cell imaging data and enables highly reproducible automated imaging. We are working to apply this imaging technology in the cell manufacturing setting to solve the two problems described above.
1-1. In-line quality control technology
The quality of manufactured cells is routinely evaluated by manual microscopic observation. However, inconsistency in cell quality cannot be prevented by this approach because of differences between observers and the possibility of overlooking abnormalities. To achieve highly consistent cell quality, quantitative in-line evaluation of cell conditions is essential. Yokogawa is working to develop technology that enables quantitative evaluation of cell conditions without sampling from the line and without damaging the cells.
This technology shows the status of several indexes, including cell growth and morphological characteristics, as quantitative values, showing the changes over time in the characteristics of cells. The quality of cultured cells is conventionally evaluated subjectively by an observer based on their experience, but with our technology, the production of cells can be controlled based on the quantitative information. This technology employs software that has learned to identify favorable and unfavorable cells from data acquired over the years using Yokogawa’s live imaging technology, enabling automated evaluation of cell quality. Such production control technology creates value in the following ways: (1) reducing labor costs and human resource costs, (2) reducing development costs, and (3) reducing the rejection rate, thereby reducing manufacturing costs.
1-2. Quality evaluation system for starting cells
Characteristics of iPS cell lines vary depending on the donor and the reprograming method. Also, the quality of the cell lines can vary depending on how they are handled. Thus, the quality of cells to be propagated must be evaluated for stable, efficient cell production. Conventionally, however, laborious tests involving cell disruption are required for evaluating cell quality. In collaboration with academia and other companies, Yokogawa is currently developing AI-assisted technology that evaluates the quality of iPS cells, which are used as starting materials for a range of cell products.
2. Cell culture technology
Technology has yet to be established for obtaining iPS-derived cells and organs that function as well as the actual cells and organs in the body, and this is another problem in cell manufacturing. Currently, cells are cultured on culture dishes under conditions different from developmental conditions. This is likely why iPS-derived cells and organs have impaired function.
Yokogawa has pursued the idea that the cell culture environment where cell signaling occurs should be similar to the physiological environment, with particular focus on the scaffold (extracellular matrix), signaling substances, and nutrients. We are currently developing cell culture technology that optimizes cell culture conditions. Examples of this technology include a system for fine modification of the cell scaffold, a system for measuring important extracellular components, and a valve mechanism enabling controlled addition of important components remotely.
Vision for the Future
Yokogawa aims to establish a cell manufacturing system that uses our in-line quality control technology in combination with our technology for optimizing cell culture conditions. This system will contribute to stable, high-quality cell manufacturing, and consequently to improved business efficiency and the development of regenerative medicine.
The cell culture process for deriving a liver or a pancreas from iPS cells, which sometimes takes more than 30 days, is complicated and requires modifying the composition of culture media. Our in-line quality control technology will stabilize the long manufacturing process and, through its non-invasive nature, contribute to increased yields. Further, our technology for optimizing cell culture conditions will offer favorable culture conditions that could not otherwise be achieved by manual quality control and conventional culture dish-based manufacturing. With this technology, cultured cells can be obtained that stably provide their expected functions.
Yokogawa will work on developing in-line quality control technology and improving the functionality of differentiated cells and tissues, aiming to expedite the progress of regenerative medicine.