Abstract

Application of glycotherapeutic agents for mesenchymal stem cell therapies

Simon Cool, Senior Principal Investigator, Institute of Medical Biology A*STAR

Adult mesenchymal stem cell (MSC) therapies are a rapidly evolving pillar of clinical medicine for treating conditions where body tissue needs to be replaced, repaired, or regenerated. These stem cells typically reside in our tissues and are administered to patients in the form of cellular infusions or incorporated into cellular grafts. Because of their small numbers in body tissues, MSCs are usually surgically isolated from patients or prospective donors and further processed to achieve the quantities needed for therapeutic use or cell banking. These processes are time-intensive and extremely costly with no guarantee that, if needed, the stem cells will be capable of sufficient ex vivo growth or remain efficacious after their extensive processing. Growth factor-based additives and natural/synthetic substrates have been trialled to increase the quantity of stem cells available for clinical use. Unfortunately these strategies can result in phenoptyic drift and a loss of clinical efficacy. Heparan sulfate (HS) glycosaminoglycan sugars are an emerging therapeutic option and are showing promise as additives in media used for the expansion of stem cells with high purity and potency. Our efforts have centred on controlling interactions between key growth factors known to be mitogenic to stem cells and their cellular receptors. By using HS agents to increase particular molecular interactions, our data is showing the power that HS exerts on the cellular microenvironment and highlights the considerable potential this strategy has for regenerative medicine.