Cross talk between 26S proteasome and mitochondria in human mesenchymal stem cells’ ability to survive under hypoxia stress

Abstract

Mesenchymal stem cells (MSCs) are regarded as unique cells which play an imperative role in the field of regenerative medicine. They are characterized by the self-renewal capacity, multi-lineage differentiation abilities and immunomodulation properties which render them perfectly ideal cell type for treating a wide range of chronic diseases. Despite these enchanted features, there are many hurdles that need to be circumvented to ensure their long-term survival and viability after transplantation. Recently, hypoxia has been indicated as one of the most baffling stress conditions that can affect the survival rate of MSCs either positively or negatively depending on the level of hypoxia. MSCs can survive well under moderate hypoxia, but die shortly if they were exposed to severe hypoxia without clearly convincing explanation for this enigma. The current study reveals a novel mechanism of 26S proteasome in controlling the ability of BM-MSCs to withstand hypoxic stress by maintaining proper mitochondrial function. The results indicated that 26S proteasome remains functioning once BM-MSCs are exposed to moderate hypoxia (2.5%O 2) and preserves their survival and proliferation mediated by intact mitochondrial performance, whereas 26S proteasome becomes inactive when BM-MSCs faces severe hypoxia that lead to poor mitochondrial function and less chance to survive longer. The outcomes of this study demonstrated the importance of 26S proteasome machinery in enhancing the resistance of BM-MSCs to hypoxic stress condition which may help in better planning future studies that target this system.

Menstrual blood-derived stromal cells: insights into their secretome in acute hypoxia conditions

“…However, the efficacy of MSCs is limited due to the poor survival rate after transplantation (Sylakowski et al 2020 ). Many studies have shown that MSCs are able to tolerate moderate hypoxia, but not the severe hypoxia that predominates in many diseases involving injured tissue (Sylakowski et al 2020 ; Khasawneh et al 2019 ). Under physiological conditions, MSCs can experience low O 2 concentrations ranging from 1 to 15% in their niche.…”

Mitohormesis and mitochondrial dynamics in the regulation of stem cell fate

“…It has been demonstrated that 26S proteasome could help MSCs to resist hypoxic conditions. When MSCs are exposed to moderate hypoxia (2.5% O 2 ), 26S proteasome remains functioning and improves MSCs survival and proliferation, whereas 26S proteasome is inactivated when MSCs experience intensive hypoxia, leading to the poor function of mitochondria and less chance of longer survival (Khasawneh et al, 2019).…”

Mesenchymal Stem Cell Exosomes in the Treatment of Myocardial Infarction: a Systematic Review of Preclinical In Vivo Studies

“…Bone marrow MSCs offer great promise for the treatment of myocardial ischemia owing to the ease with which they can be isolated, cultured, and expanded while maintaining important stem cell properties [64]. Researchers initially hypothesized that transplanted MSCs would be able to differentiate into cardiomyocytes and vascular endothelial cells, but more recent evidence suggests that the majority of transplanted cells die within a month under hypoxic conditions within the ischemic microenvironment, while their differentiation cannot be effectively controlled [65].…”