Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine.
The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal
lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been
described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to
suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by
reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical
reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase
isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact
with several pathways that affect the transcription machinery required for MSC differentiation including the
Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative
stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical
for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS
implicated remain to be determined. This review provides a detailed overview of the influence of ROS on
adipogenic and osteogenic differentiation in MSCs.