Faculty Indian Institute of Science Education and Research, India
Abstract: For successful transplantation therapy, it is a prerequisite that MSCs migrate and home in adequate numbers to the site of tissue damage marked by adverse microenvironment conditions. Thus, it is pivotal to identify novel factors and their mechanism of action in regulating the adhesion and migration of MSCs under different microenvironment stress conditions. Our study in human placenta-derived MSCs (PL-MSCs) under nutrient stress demonstrated an increase in cell spread area, increased adhesion, and reduced migration of the cells. Correspondingly, an increase in the total number and size of focal adhesions (FAs), along with prominent stress fibers, were observed. Furthermore, the FAs in nutrient-stressed MSCs were more stable, exhibiting slower turnover and longer lifespan. Vitronectin (VTN), an ECM glyocprotein, was upregulated under nutrient stress condition. Knockdown of VTN under nutrient stress condition led to a significant reduction in the total number and size of FAs along with their faster turnover and shorter lifespan. Subsequently, a reversal in the cell spread area and the adhesion and migration properties of the PL-MSCs were noted. Additionally, our findings indicated that VTN, acting upstream, influenced the phosphorylation of myosin light chain (MLC), promoted the maturation and stability of FAs, and generated organized stress fibers. Overall, our study identifies a new role of VTN as a critical regulator of adhesion and migration in PL-MSCs under nutrient stress condition.
