학술논문

Serum starvation affects mitochondrial metabolism of adipose-derived stem/stromal cells.
Document Type
Article
Source
Cytotherapy (Elsevier Inc.). Jul2023, Vol. 25 Issue 7, p704-711. 8p.
Subject
*STROMAL cells
*RESPIRATION
*MITOCHONDRIA
*METABOLISM
*SUCCINATE dehydrogenase
*STARVATION
*SLEEP deprivation
*METABOLOMICS
Language
ISSN
1465-3249
Abstract
A large part of mesenchymal stromal cell (MSC) regenerative and immunomodulatory action is mediated by paracrine signaling. Hence, an increasing body of evidence acknowledges the potential of MSC secretome in a variety of preclinical and clinical scenarios. Mid-term serum deprivation is a common approach in the pipeline of MSC secretome production. Nevertheless, up to now, little is known about the impact of this procedure on the metabolic status of donor cells. Here, through untargeted differential metabolomics, we revealed an impairment of mitochondrial metabolism in adipose-derived MSCs exposed for 72 h to serum deprivation. This evidence was further confirmed by the significant accumulation of reactive oxygen species and the reduction of succinate dehydrogenase activity. Probably as a repair mechanism, an upregulation of mitochondrial superoxide dismutase was also induced. Of note, the analysis of mitochondrial functionality indicated that, despite a significant reduction of basal respiration and ATP production, serum-starved MSCs still responded to changes in energy demand. This metabolic phenotype correlates with the obtained evidence of mitochondrial elongation and branching upon starvation. [Display omitted] • Serum starvation is a common upstream procedure of secretome collection. • Mid-term serum withdrawal affects MSC metabolome, mostly at mitochondrial level. • Mitochondrial impairment is confirmed by ROS accumulation and SDH downregulation. • MSCs react to oxidative stress by increasing SOD2 expression. • Upon starvation, MSCs reduce basal respiration and show elongated mitochondria. [ABSTRACT FROM AUTHOR]