The Role of Reactive Oxygen Species in Mesenchymal Stem Cell Adipogenic and Osteogenic Differentiation: A Review

Abstract

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.

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Insights Into Signaling in Cell-Based Therapy for Heart Disease

“…High ROS levels in stem cells cause damage and dysfunction, but a low basal level of ROS is necessary for maintaining cellular proliferation, differentiation, and survival. 193,194 Multiple studies using different disease models [195][196][197][198] demonstrated that MSC could exert an antioxidative effect leading to a decrease in severity of organ injury. 199 This effect is primarily regulated through secretion of soluble factors, which prevent ROS accumulation through enhanced scavenging and antioxidant upregulation.…”

Gold nanoparticles promote osteogenic differentiation in human adipose-derived mesenchymal stem cells through the Wnt/β-catenin signaling pathway

“…31 In particular, excessive ROS cause damage to MSCs, whereas low levels of ROS enhance osteogenesis of MSCs. 32 To determine the viability of hADMSCs treated with chitosan-conjugated AuNPs, cell viability assays were performed for 72 hours in a growth medium that did not contain osteogenic-inducing substances ( Figure 2A). As shown in Figure 2A, chitosan-conjugated AuNPs had no effect on the cell viability of hADMSCs at a concentration of up to 10 ppm.…”