Changes in Expression of the Antioxidant Enzyme SOD3 Occur Upon Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells In Vitro

Abstract

The discovery that mesenchymal stem cells (MSCs) secrete SOD3 may help explain studies in which MSCs have direct antioxidant activities both in vivo and in vitro. SOD3 is an antioxidant enzyme that dismutes toxic free radicals produced during inflammatory processes. Therefore, MSC production and secretion of active and therapeutically significant levels of SOD3 would further support the use of MSCs as a cellular based antioxidant therapy. The aim of this study was therefore to investigate in vitro if MSC differentiation down the adipogenic, chondrogenic, and osteogenic lineages influences the expression of the antioxidant molecule SOD3. Human bone marrow MSCs and their differentiated progeny were cultured under standard conditions and both the SOD3 gene and protein expression examined. Following adipogenesis, cultures demonstrated that both SOD3 protein and gene expression are significantly increased, and conversely, following chondrogenesis SOD3 protein and gene expression is significantly decreased. Following osteogenesis there were no significant changes in SOD3 protein or gene expression. This in vitro study describes the initial characterization of SOD3 expression and secretion by differentiated MSCs. This should help guide further in vivo work establishing the therapeutic and antioxidative potential of MSC and their differentiated progeny.

Modulating the oxidative environment during mesenchymal stem cells chondrogenesis with serum increases collagen accumulation in agarose culture

“…The reduction in glutathione (Fig. A) during early MSCs chondrogenesis suggests that increases in intracellular ROS are at least in part due to downregulation of endogenous antioxidants, which has been previously reported for MSCs chondrogenesis and superoxide dismutase . Moderate levels of ROS can act as important secondary messengers that influence stem cell survival, migration, and differentiation .…”

Oxidative stress, redox regulation and diseases of cellular differentiation

“…There are three metal containing isoforms of SOD found in different cellular compartments [38]: SOD1 (copper-zinc SOD) is in the cytoplasm, nucleus and plasma membrane; SOD2 (manganese SOD) is mainly in mitochondria [5]; and SOD3 (copper-zinc SOD) is unique in scavenging superoxide in the extracellular compartment, dismutating superoxides generated during the inflammatory cascade [39]. Bone marrow-derived human mesenchymal stem cells (MSC) specifically secrete SOD3 directly promoting cell survival by reducing toxic ROS [40].…”

“…Bone marrow-derived human mesenchymal stem cells (MSC) specifically secrete SOD3 directly promoting cell survival by reducing toxic ROS [40]. MSC differentiation through the adipogenic, chondrogenic, and osteogenic lineages influences the expression of SOD3 [39]. SOD operates in conjunction with catalase to maintain hydrogen peroxide levels resulting from SOD catalysis.…”

Degradation of alkanethiol self‐assembled monolayers in mesenchymal stem cell culture

“…It has previously been shown that SAMs can have a protective effect on metal surfaces, helping to slow down oxidation, which may help to protect against cell‐induced degradation of the Au. Additionally, in contrast to many other cell types, mesenchymal stem cells are known to inhibit oxidative processes, secreting the enzyme superoxide dismutase 3 (SOD3), an antioxidant enzyme that catalyzes the reduction of superoxides . It is also possible that the nonproliferative state of the HMSCs induced to enable appropriate cell counting in these studies affects the production of SAM‐degrading factors.…”

“…Additionally, in contrast to many other cell types, mesenchymal stem cells are known to inhibit oxidative processes, secreting the enzyme superoxide dismutase 3 (SOD3), an antioxidant enzyme that catalyzes the reduction of superoxides. 65 It is also possible that the nonproliferative state of the HMSCs induced to enable appropriate cell counting in these studies affects the production of SAM-degrading factors. HMSCs on 4 and 10 nm Au began to migrate away from their initial confinement to the originally SAM coated regions at 5 days with 53.0% 6 11.7% and 2.5% 6 0.0% of cells migrating, respectively.…”