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

## TL;DR

This paper shows that miR-18a-5p prevents aging in stem cells by controlling CTDSPL, which helps maintain their function during long-term lab cultivation.

## Contribution

The study reveals a novel regulatory interaction between miR-18a-5p and CTDSPL in preventing mesenchymal stem cell senescence.

## Key findings

- Overexpression of CTDSPL leads to enlarged morphology and cell cycle arrest in MSCs.
- miR-18a-5p inhibits CTDSPL, reducing ROS levels and promoting stem cell self-renewal.
- Inhibition of miR-18a-5p induces premature senescence in MSCs.

## Abstract

Stem cell therapy requires massive-scale homogeneous stem cells under strict qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in the premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renewal ability of MSCs. Over-expression of CTDSPL resulted in 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 that CTDSPL induced premature senescence of MSCs. We further demonstrated that 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 reducing ROS level, increased expression of Oct4 and Nanog, and promoted growth rate and differentiation capability. We reported for the first time that the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.