Proteomics

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NAD+/NADH Redox Alterations Reconfigure Metabolism and Rejuvenate Senescent Human Mesenchymal Stem Cells In Vitro


ABSTRACT: Human mesenchymal stem cells (hMSCs) promote endogenous tissue regeneration and have become a promising candidate for cell therapy. However, in vitro culture expansion of hMSCs induces a rapid decline of stem cell properties through replicative senescence. Here we characterize metabolic profiles of hMSCs during expansion. We show that alterations of cellular nicotinamide adenine dinucleotide (NAD+ /NADH) redox balance and activity of the Sirtuin (Sirt) family enzymes regulate cellular senescence of hMSCs. Treatment with NAD+ precursor nicotinamide increases the intracellular NAD+ level and re-balances the NAD+ /NADH ratio, with enhanced Sirt-1 activity in hMSCs at high passage, partially restores mitochondrial fitness and rejuvenates senescent hMSCs. By contrast, human fibroblasts exhibit limited senescence as their cellular NAD+ /NADH balance is comparatively stable during expansion. These results indicate a potential metabolic and redox connection to replicative senescence in adult stem cells and identify NAD+ as a metabolic regulator that distinguishes stem cells from mature cells. This study also suggests potential strategies to maintain cellular homeostasis of hMSCs in clinical applications.

INSTRUMENT(S): LTQ Orbitrap, 6340 Ion Trap LC/MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell

SUBMITTER: Xuegang Yuan  

LAB HEAD: Yan Li

PROVIDER: PXD022395 | Pride | 2021-09-09

REPOSITORIES: Pride

Dataset's files

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Action DRS
P12vsP4.xls Xls
P12vsp4.xlsx Xlsx
P8vsP4.xls Xls
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Publications

NAD<sup>+</sup>/NADH redox alterations reconfigure metabolism and rejuvenate senescent human mesenchymal stem cells in vitro.

Yuan Xuegang X   Liu Yijun Y   Bijonowski Brent M BM   Tsai Ang-Chen AC   Fu Qin Q   Logan Timothy M TM   Ma Teng T   Li Yan Y  

Communications biology 20201215 1


Human mesenchymal stem cells (hMSCs) promote endogenous tissue regeneration and have become a promising candidate for cell therapy. However, in vitro culture expansion of hMSCs induces a rapid decline of stem cell properties through replicative senescence. Here, we characterize metabolic profiles of hMSCs during expansion. We show that alterations of cellular nicotinamide adenine dinucleotide (NAD + /NADH) redox balance and activity of the Sirtuin (Sirt) family enzymes regulate cellular senescen  ...[more]

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