Abstract
Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and developing strategies to enhance treatment efficacy. Different paradigms have been constructed to explain their mechanism of action, including tissue regeneration, trophic/anti‐inflammatory secretion, and immunomodulation. MSCs rarely engraft and differentiate into other cell types after in vivo administration. Furthermore, it is equivocal whether MSCs function via the secretion of many peptide/protein ligands as their therapeutic properties are observed across xenogeneic barriers, which is suggestive of mechanisms involving mediators conserved between species. Oxidative stress is concomitant with cellular injury, inflammation, and dysregulated metabolism which are involved in many pathologies. Growing evidence supports that MSCs exert antioxidant properties in a variety of animal models of disease, which may explain their cytoprotective and anti‐inflammatory properties. In this review, evidence of the antioxidant effects of MSCs in in vivo and in vitro models is explored and potential mechanisms of these effects are discussed. These include direct scavenging of free radicals, promoting endogenous antioxidant defenses, immunomodulation via reactive oxygen species suppression, altering mitochondrial bioenergetics, and donating functional mitochondria to damaged cells. Modulation of the redox environment and oxidative stress by MSCs can mediate their anti‐inflammatory and cytoprotective properties and may offer an explanation to the diversity in disease models treatable by MSCs and how these mechanisms may be conserved between species.
Highlights
Mesenchymal stem cells have been used as tools to treat a broad range of diseases in animal models due to their unique characteristics such as host immune evasion, rapid expansion, and their affluence in adult bone marrow and adipose tissue
mesenchymal stem cells (MSCs) exposed to hypoxic conditions (1.5%-2% O2) exhibit increased intracellular reactive oxygen species (ROS) and cells respond by upregulating the expression of hypoxiainducible factor 1 alpha (HIF-1α), erythropoietin receptor, CAT, TABLE 1 Antioxidant activity of MSCs in disease models
In endothelial cells, increased SOD2 expression was regulated by signal transducer and activator of transcription (STAT3) signaling and knockdown of either SOD2 or signal transducer and activator of transcription 3 (STAT3) decreased the antiapoptotic effects of the MSC-conditioned medium (CM).[77]. These findings suggest that MSC upregulation of superoxide dismutase (SOD) in host tissues may be critical to their antioxidant effects
Summary
Mesenchymal stem cells (multipotent stromal cells; MSCs) have been used as tools to treat a broad range of diseases in animal models due to their unique characteristics such as host immune evasion, rapid expansion, and their affluence in adult bone marrow and adipose tissue. MSCs were explored as tools of regenerative medicine to replace damaged tissue.[2] administered MSCs were rarely observed to differentiate and effectively engraft into host tissues despite demonstrating favorable effects in many disease models.[3] the secretome of MSCs was identified to be therapeutic in many disease models in vitro and in vivo Together, this resulted in a paradigm shift in recognition of the trophic actions of MSCs.[4] Despite extensive research investigating the anti-inflammatory and trophic constituents of the MSC-derived secretome, the therapeutic mechanisms of MSCs remain incompletely resolved.[5] MSCs demonstrate therapeutic attributes across xenogeneic barriers and, the therapeutic mechanisms of MSCs may be similar between species. Oxidative stress refers to a deviation from the physiological redox state and an increase in pro-oxidants, or free radicals, that structurally
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
