Stem cells are a promising cell source for regenerative medicine. Stem cell differentiation must be regulated for applications in regenerative medicine. Stem cells are surrounded by extracellular matrix (ECM) in vivo. The ECM is composed of many types of proteins and glycosaminoglycans that assemble into a complex structure. The assembly of ECM molecules influences stem cell differentiation through orchestrated intracellular signaling activated by many ECM molecules. Therefore, it is important to understand the comprehensive role of the ECM in stem cell differentiation as well as the functions of the individual ECM molecules. Decellularized ECM is a useful in vitro model for studying the comprehensive roles of ECM because it retains a native-like structure and composition. Decellularized ECM can be obtained from in vivo tissue ECM or ECM fabricated by cells cultured in vitro. It is important to select the correct decellularized ECM because each type has different properties. In this review, tissue-derived and cell-derived decellularized ECMs are compared as in vitro ECM models to examine the comprehensive roles of the ECM in stem cell differentiation. We also summarize recent studies using decellularized ECM to determine the comprehensive roles of the ECM in stem cell differentiation.

Stem cell differentiation is an important issue in regenerative medicine and tissue engineering. It has been reported that cell shape is one of the factors that determine the lineage commitment of mesenchymal stem cells (MSCs). Therefore, the substrates have been developed to control their shapes. Recently, we found that poly(2-methoxyethyl acrylate) (PMEA) analogs can control tumor cell shape through the alteration of protein adsorption. Here, the adipogenesis of an adipocyte-progenitor cell, 3T3-L1 cells, was attempted; adipogenesis was to be regulated by surfaces coated with PMEA analogs through the control of their shape. The adipogenesis of 3T3-L1 cells was promoted on the surfaces coated with PMEA and its analogs, PMe3A and PMe2A. Evident focal adhesions were hardly observed on these surfaces, suggesting that integrin signal activation was suppressed. Additionally, actin assembly and cell spreading were suppressed on these surfaces. Therefore, the surfaces coated with PMEA analogs are expected to be suitable surfaces to regulate adipogenesis through the suppression of cell spreading. Additionally, we found that protein adsorption correlated with actin assembly and adipogenesis.

Circulating tumor cells (CTCs) have been a focus of study for metastatic cancer diagnostics, in in vitro anti-cancer drug screening to decide the chemotherapeutic course, and cancer biology research.