(371p) Computer-Aided Exploration of Cryoprotective Agents for Stem Cell Manufacturing

Stem cell therapy has recently emerged as a key player in regenerative medicine. Along with recent successful clinical studies using stem cells, the implementation of stem-cell-based medical treatments is in progress. In stem cell manufacturing, freezing processes are one of the most critical steps because the process is needed to the transportation and preservation of the cells. Cryoprotective agents (CPAs) are used to protect cells from freezing injuries. Dimethyl sulfoxide (DMSO) was discovered to have cryoprotective effects and is still widely used today, although DMSO is toxic to stem cells and has the property of acting as a differentiation factor¹. Thus, it is urgently needed to develop alternative compounds for DMSO.

In the field of process systems engineering, computer-aided molecular design (CAMD) and large-scale screening have been intensively explored. Liu et al.² developed a computer-aided toolbox for molecular and mixture product design problems. Ten et al³ presented a CAMD framework by incorporating safety and occupational health aspects. Valencia-Marquez et al.⁴ proposed a CAMD approach for an ionic liquid-based lubricant. However, regarding CPAs, CAMD and large-scale screening are yet to be applied.

This work presents an exploration of CPAs for stem cell manufacturing using CAMD approaches that can comprehensively consider compounds. From a CAMD perspective, it is necessary to convert requirements into physical properties, although it is unclear which properties are related to cryoprotective effects. Therefore, we developed an exploration cycle that can expose better candidates by incorporating domain knowledge through discussions with experts from the field of biotechnology.

The developed cycle was performed twice for exploration of CPAs. As a result, 1-methylimidazole and pyridazine were selected as promising CPA candidates, which were both heterocyclic amines. By using the exploration cycle repeatedly, CPA candidates with better cryoprotective effects would be discovered. In future, the third application of the cycle focusing on heterocyclic amines could lead to exposing more effective CPA candidates.

References

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2. Liu Q, Zhang L, Liu L, Du J, Tula AK, Eden M, Gani R. OptCAMD: An optimization-based framework and tool for molecular and mixture product design. Comput. Chem. Eng. 2019;124:285–301.

3. Ten, JY, Hassim, MH, Chemmangattuvalappil, NG. Integration of safety and health aspects in a simultaneous process and molecular design framework. Chem. Eng. Res. Des. 2020; 153:849–864.

4. Valencia-Marquez D, Flores-Tlacuahuac A, García-Cuéllar AJ, Ricardez-Sandoval L. Computer aided molecular design coupled with molecular dynamics as a novel approach to design new lubricants. Comput. Chem. Eng. 2022;156:107523.