Recent Advances in Monitoring Stem Cell Status and Differentiation Using Nano-Biosensing Technologies.

In regenerative medicine, cell therapies using various stem cells have received attention as an alternative to overcome the limitations of existing therapeutic methods. Clinical applications of stem cells require the identification of characteristics at the single-cell level and continuous monitoring during expansion and differentiation. In this review, we recapitulate the application of various stem cells used in regenerative medicine and the latest technological advances in monitoring the differentiation process of stem cells. Single-cell RNA sequencing capable of profiling the expression of many genes at the single-cell level provides a new opportunity to analyze stem cell heterogeneity and to specify molecular markers related to the branching of differentiation lineages. However, this method is destructive and distorted. In addition, the differentiation process of a particular cell cannot be continuously tracked. Therefore, several spectroscopic methods have been developed to overcome these limitations. In particular, the application of Raman spectroscopy to measure the intrinsic vibration spectrum of molecules has been proposed as a powerful method that enables continuous monitoring of biochemical changes in the process of the differentiation of stem cells. This review provides a comprehensive overview of current analytical methods employed for stem cell engineering and future perspectives of nano-biosensing technologies as a platform for the in situ monitoring of stem cell status and differentiation.