Restoration of mesenchymal stem cell function using pharmacological agents

Abstract

The extensive characteristics of mesenchymal stem cells (MSCs), especially their capacity to replicate and differentiate into any type of fully developed cell make these cells suitable for use in cell therapy. These cells are clinically introduced into a tissue in an autologous or allogeneic manner for the treatment of inflammatory and degenerative diseases with or without gene therapy. There are however, some drawbacks related to the clinical use of MSCs, with one major limitation being that these cells tend to decrease in 'sternness' and quantity with increasing donor age and disease while the underlying mechanisms of stem cell ageing remain vague. An increased activity of the small RhoGTPase Cdc42 is thought to play a key modulatory role in MSC ageing. Cdc42 activity is known to partake in the regulation of numerous signaling pathways and also cause depolarization of planer cell polarity markers hence has been identified as a pharmacological target for improving MSC ageing. The aim of this study is to investigate the regulatory effect of small molecule on Cdc42 activity in MSCs.