Cordycepin EnhancesSIRT1Expression and Maintains Stemness of Human Mesenchymal Stem Cells

Abstract

Background/Aim: Mesenchymal stem cells (MSCs) have been employed for therapeutic applications of various degenerative diseases. However, the major concern is MSC aging during the in vitro cultivation. Thus, the approach to delay MSC aging was examined in this research by focusing on the expression of Sirtuin 1 (SIRT1), a key anti-aging marker. Materials and Methods: Cordycepin, a bioactive compound derived from Cordyceps militaris, was used to up-regulate SIRT1 and maintain stemness of MSCs. Upon treatment with cordycepin, MSCs were investigated for cell viability, doubling time, key gene/protein expression, galactosidase-associated senescence assay, relative telomere length, and telomerase expression. Results: Cordycepin significantly increased the expression of SIRT1 in MSCs by activating the adenosine monophosphate activated protein kinase (AMPK)-SIRT1 signalling pathway. Moreover, cordycepin maintained the stemness of MSCs by deacetylating SRY-box transcription factor 2 (SOX2) via SIRT1, and cordycepin delayed cellular senescence and aging of MSCs by enhancing autophagy, inhibiting the activity of senescence-associated-galactosidase, maintaining proliferation rate, and increasing telomere activity. Conclusion: Cordycepin could be used to increase SIRT1 expression in MSCs for anti-aging applications.Regenerative medicine and cell therapy are modern medical advancements that are gaining a lot of attention as novel methods for treating severe diseases (1). MSCs are used to treat a variety of degenerative diseases, such as cardiovascular diseases, neuro degenerative diseases, bone and cartilage diseases, cancers, liver diseases, kidney diseases, and autoimmune diseases [including: graft versushost diseases, multiple sclerosis, Crohn's disease, type1 diabetes, systemic lupus erythematous, rheumatoid arthritis] (2). MSCs are adult stem cells that can be obtained from the bone marrow, adipose tissue, umbilical cord tissue, and umbilical cord blood (3). MSCs can differentiate into a variety of cells, including adipocytes, osteoblasts, chondrocytes, endothelial cells, and cardiomyocytes (4). MSCs have the capacity for selfrenewal and multipotency (5), and play a significant role in the development of specific organs and tissues with special functions (6). However, MSC aging is a critical problem that contributes to the loss of self-renewal, stemness and differentiation potential (7). MSCs are ineligible to be used in regenerative medicine treatments after prolonged in vitro cultivation because their selfrenewal and multipotency declines (8). Additionally, replicative senescence influences long-term changes in phenotype, differentiation potential, whole-map gene expression patterns, and microRNA profiles, all of which should be taken into consideration as therapeutic targets for MSC rejuvenation (9). Therefore, an appropriate method to maintain the self-renewal and multipotency of MSCs is very important for their use in therapeutic applications.SIRT1 is a nicotinamide adenine dinucleotide (NAD+)dependent lysine deacet...