Successful cultivation of stem cells on the surface of ionic liquids

1. The National Institute for Materials Science (NIMS) has established a technique for cultivating human mesenchymal stem cells, widely used in regenerative medicine, on the surface of a liquid known as “ionic liquid.” This innovation promises a significant increase in the efficiency of cell culturing valuable cellular resources, traditionally carried out in plastic dishes, while also reducing plastic waste generated during culturing. Ionic liquids, which do not evaporate, prevent environmental diffusion. Unlike disposable plastic dishes, these liquids can be recovered, cleaned, and sterilized through heating/drying for reuse, marking a vital step towards an environmentally friendly reusable “liquid” cell culture substrate.

2. Conventionally, the culturing and proliferation of (stem) cells suitable for applications such as regenerative medicine utilize solid plastic dishes. Cell culturing on the surface of a liquid, like oil that does not mix with water, has been a long-researched concept due to its potential to significantly increase the efficiency of culturing per unit volume by dispersing the liquid in the culture solution like “salad dressing”. Not only does this approach reduce the ever-increasing plastic waste, but it also paves the way for technological innovations, such as cell separation/recovery through filtration leveraging liquid properties and complete automation of the cell culturing process. However, fluorinated liquids used in the research field, although less cytotoxic, have been highlighted for their low chemical degradability in the environment, bringing attention to the “forever chemicals” or “PFAS issue” and raising concerns about the high costs and environmental impact as a trade-off for advancing cell culture technology.

3. The NIMS research team has now successfully cultured human mesenchymal stem cells on the surface of ionic liquids, which do not mix with water and exhibits extremely low cytotoxicity. Ionic liquids consist solely of positive and negative ions and are characterized by their non-evaporating and non-volatile property. After cell culture, the liquid can be cleaned, heated, dried, and sterilized, allowing for reuse instead of disposal. Further, the research group discovered that the combination of ions in the ionic liquid significantly changes the adsorption state of proteins on the liquid surface, which is crucial in forming superior liquid scaffolds.

4. Moving forward, the team aims to establish techniques to control the differentiation state of stem cells on the ionic liquid surface, improve the culturing efficiency of valuable stem cell resources through dispersion culture, and develop a culturing process that does not produce plastic waste. The team will continue to advance the development of cleaning and sterilization processes for ionic liquids suitable for cell culture.

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5. This research is the result of the efforts by Senior Researcher Takeshi Ueki and Group Leader Jun Nakanishi of the Research Center for Macromolecules and Biomaterials, supported by the Japan Society for the Promotion of Science’s Grants-in-Aid for Scientific Research (23H02030 (Representative: Takeshi Ueki), 22H00596, and 23K17481 (Representative: Jun Nakanishi)).

6. The results of this study were published online in the journal Advanced Materials on February 26, 2024. (T. Ueki et al., Adv. Mater., 2024, 2310105.)