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Review
. 2021 Jun 17;10(6):973.
doi: 10.3390/antiox10060973.

NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

Tullia Maraldi  1 , Cristina Angeloni  2 , Cecilia Prata  3 , Silvana Hrelia  4
Affiliations
Review

NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function

Tullia Maraldi et al. Antioxidants (Basel). .

Abstract

One of the major sources of reactive oxygen species (ROS) generated within stem cells is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (NOXs), which are critical determinants of the redox state beside antioxidant defense mechanisms. This balance is involved in another one that regulates stem cell fate: indeed, self-renewal, proliferation, and differentiation are decisive steps for stem cells during embryo development, adult tissue renovation, and cell therapy application. Ex vivo culture-expanded stem cells are being investigated for tissue repair and immune modulation, but events such as aging, senescence, and oxidative stress reduce their ex vivo proliferation, which is crucial for their clinical applications. Here, we review the role of NOX-derived ROS in stem cell biology and functions, focusing on positive and negative effects triggered by the activity of different NOX isoforms. We report recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment and discuss the implications in ex vivo expansion and in vivo engraftment, function, and longevity. This review highlights the role of NOX as a pivotal regulator of several stem cell populations, and we conclude that these aspects have important implications in the clinical utility of stem cells, but further studies on the effects of pharmacological modulation of NOX in human stem cells are imperative.

Keywords: NADPH oxidases; reactive oxygen species; stem cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Metabolic and redox changes during stem cell life. Regulation of self-renewal, differentiation, and reprogramming by NOX-derived ROS beside glycolytic metabolism for embryonic, fetal, and adult stem cells. Image created with BioRender.com (accessed on 1 May 2021).
Figure 2
Figure 2
Summary of the involvement of NOX isoforms in different types of stem cells. Image created with BioRender.com (accessed on 1 May 2021).
See this image and copyright information in PMC

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