Analysis of Metabolomic Changes in Mesenchymal Stem Cells on Treatment with Desferrioxamine as a Hypoxia Mimetic Compared with Hypoxic Conditions

Abstract

Mesenchymal stem cells (MSCs) are commonly used in regenerative medicine, but their therapeutic effects vary depending on the culture environment. Hypoxic culturing can be used to maintain stem cells in an undifferentiated state, but is expensive and difficult to perform. The aim of this study was to determine the effectiveness of desferrioxamine (DFO), a hypoxia-mimetic reagent, as an alternative to hypoxic culturing by analyzing metabolic changes in MSCs under hypoxic conditions compared with changes induced by DFO. Low concentrations of DFO reduced mitochondrial activity and apoptosis. Therefore, low concentrations of DFO may be useful for MSC preconditioning. Metabolome analysis showed that both hypoxic treatment and DFO administration exhibited similar metabolite patterns except purine, pyrimidine, and tricarboxylic acid cycle (TCA) cycle related metabolites. Therefore, the use of DFO at low concentrations is a potential substitute for hypoxic culturing. These findings may form the foundation for the development of future regenerative therapies using MSCs. Stem Cells 2018;36:1226–1236.