MicroRNA-18a prevents senescence of mesenchymal stem 2 cells by targeting CTDSPL

Stem cell therapy requires massive scale homogeneous stem cells under strictly qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). In this study, we revealed the up-regulations of CTDSPL in prolonged culture of MSCs derived from human umbilical cord (UCMSCs). Over-expression of CTDSPL resulted an enlarged morphology, up-regulation of p16 and accumulation of SA-β-gal of MSCs. The reduced phosphorylated RB suggested cell cycle arrest of MSCs. All these results implied CTDSPL induced premature senescence of MSCs. We further demonstrated miR-18a-5p was a putative regulator of CTDSPL by luciferase reporter assay. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reduced ROS level, increased expression of Oct4 and Nanog, promoted growth rate and differentiation capability. Hereby, we reported for the first time the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.