Morphology-based early profiling of chemical compound effects on mesenchymal stem cell

Abstract

Currently, various protocols have been developed to differentiate stem cells into target cells for applications in regenerative medicine and drug discovery. In many protocols, factors to control cellular differentiation are now replaced by small chemical compounds by their stable and cost- effective performance compared to protein-based factors. There are also reports that indicate such differentiation controlling compounds can be used as medical drug seed molecules. Therefore, great attention is attracted in screening chemical compounds that stimulate stem cells either negatively/positively. However, the evaluation of such compounds for stem cell culture is time-consuming, costly, and cell-invasive (endpoint assay). In our group, we have been applying image processing and bioinformatics analysis for quantitative evaluation of cellular phenotypic changes, such as evaluation of cellular quality during their culture process. In this study, we have applied this evaluation technique to assay the stem cell response to the small compounds rapidly, cost-effectively, and non-invasively (real-time assay). By converting the phase contrast microscopic images of cells into multiple parameters, designated as "fingerprint", we found that cellular response to positive/negative stimulating compounds could be quantitatively assessed, and in some conditions, their differentiation controlling potential could be screened in extremely early stage. Our image-based early evaluation method demonstrates high potential to be applied for screening useful compound that enhance stem cell culture.