ROS and Oxidative Stress in Stem Cells

Abstract

Reactive oxygen species (ROS) are well known to be implicated in various important cellular processes including signaling, regulation of homeostasis, or induction of death. Oxidative stress resulting from increased ROS production and impaired free radical scavenging systems can cause severe damage to biological macromolecules, affecting cell proliferation and causing genomic instability and cellular senescence. Although ROS are involved in a wide range of cellular processes, a limited number of studies have examined the generation and function of ROS in stem cells. It is known that ROS may enhance differentiation of stem cells and facilitate reprogramming into induced pluripotent stem cells (iPSCs), but on the other hand, they are also associated with malignant transformation or premature aging. Stem cells have also been shown to possess defective DNA repair machinery, which may have serious consequences for cells exposed to extensive oxidative stress. Since stem cells are considered as a promising tool in regenerative medicine, it is crucial to know and better understand all the processes related to ROS to prevent potential generation of mutations causing genomic instability and to avoid unwanted ROS-driven differentiation. Thus, the mechanisms by which genomic integrity of stem cells is maintained under oxidative stress and the role of ROS should be elucidated before stem cells finally find their place in clinical applications.The paper by C.-J. Li et al. demonstrates that treatment with antioxidants not only increases proliferation and mitochondrial integrity of human mesenchymal stem cells (hMSCs) but also enhances the therapeutic potential of hMSCs by promoting the formation of tunneling nanotubes (TNTs) between hMSCs and oxidatively injured cells in a coculture system. The authors demonstrate that TNTs enable hMSCs to "export" their healthy mitochondria to the injured cells and hence decrease their oxidative stress and stabilize the mitochondrial membrane potential of the injured cells. Concurrently, the rescued cells also show enhanced mitophagy, implicating that their damaged mitochondria are eliminated in order to maintain normal cell physiology. The findings highlight that antioxidants enhance mitochondrial transfer from hMSCs to the injured cells and provide them with a repair mechanism.A similar topic is presented by Y.-C. Chuang et al. who show that Wharton's jelly mesenchymal stem cells (WJMSCs) are able to transfer healthy mitochondria to cybrid cells from a patient with myoclonus epilepsy associated with ragged-red fibers (MERRF) through intercellular connections. This mitochondrial transfer is found to be

MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro

“…We reveal that MMP9 mediates ROS-generation in hCSCs. It is known that ROS induces oxidative stress in stem cells 23 , and H 2 O 2 is an inducer of cellular oxidative stress 24 that promotes apoptosis 43 in stem cells. Our results show that hyperglycemia increases ROS production in hCSCs, which is prevented by targeted deletion of the MMP9 gene.…”

“…ROS-induced oxidative stress promotes apoptotic cell death in stem cells 23 . To determine whether the ablation of MMP9 prevents oxidative stress-induced cell death in hCSCs, we treated hCSCs and MMP9 −/− hCSCs with hydrogen peroxide (H 2 O 2 ), an inducer of oxidative damage 24 , and evaluated apoptosis and pyroptosis.…”

Impaired Regulation of Redox Transcriptome during the Differentiation of iPSCs into Induced Cardiomyocytes (iCMs)

“…Under normal/unstressed conditions, RCS play a key role in cellular physiological signaling and regulate normal cellular processes such as induction of proliferation, cell-cycle, and differentiation (23, 24). However, an excessive accumulation of RCS induces oxidative stress leading to apoptotic, necrotic and fibrotic events (25, 26).…”

“…However, an excessive accumulation of RCS induces oxidative stress leading to apoptotic, necrotic and fibrotic events (25, 26). In fact, RCS signaling is necessary for the differentiation of iPS into iCM (23, 27), but a chronic increase in RCS is detrimental to these cells as it could impair both the proliferation and differentiation processes (24, 25). Real time quenching of RCS is vital to maintain redox homeostasis, which is often controlled through multiple biochemical events.…”

UV radiation in HCT 116 cells influences intracellular H2O2 and glutathione levels, antioxidant expression, and protein glutathionylation

“…Oxidative stress is one of the external factors that influence human health (Cieślar-Pobuda et al, 2017). Maintaining a similar level between the oxidation and reduction processes in tissues and cells is called a redox equilibrium (Buldak et al, 2015).…”