INVESTIGATING SENESCENCE ASSOCIATED CHANGES IN THE HUMAN MESENCHYMAL STEM CELL HEPARANOME

Abstract

Human mesenchymal stem cells (MSCs) have gained popularity over the last decade as promising cell therapy candidates. However, clinical translation of MSC-based autologous or allogeneic therapies remains poor. The limited lifespan of these cells in vitro, owing to an acquisition of replicative senescence and an associated functional decline, pose significant challenges for cell banking and expansion processes prior to clinical application. In this regard, this project adopts a glycomics-centric approach to better characterise and understand a replicative senescence phenotype in culture-expanded MSCs. The data presented in this thesis highlight that replicative senescence in culture-expanded MSCs is accompanied by modulations in the heparanome, underpinned by changes at genomic, proteomic and glycomic levels.