Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway

Abstract

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

Curcumin Nanofiber PCL/PLGA/Collagen Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cells against Liver Fibrosis in Animal Model and Prevented its Recurrence

“…The senescence of MSCs is an obstacle against its clinical application, in the current study the survival of cur + /nanoscaffold primed MSCs was observed up to 24 th weeks in the liver tissue mainly around the portal vein compared to 12 th week in rats treated with cur - /nanoscaffold MSCs (Khuu et al reported that only small portion of MSCs engraft the liver after surgical hepatectomy and persist only for 8 weeks 41 and this may be due to the high efficacy of cur to enhance the migration and proliferation of the cells and this could explain the maintaining and protective efficacy of cur + /nanoscaffold primed MSCs. Supportive to our results, a recent study reported that cur ameliorate the senescence of MSCs through modulating autophagy pathway 42 .…”

Engineering Multifunctional Hydrogel‐Integrated 3D Printed Bioactive Prosthetic Interfaces for Osteoporotic Osseointegration

“…[ 8 ] Autophagy maintains the stemness and differentiation ability of stem cells. [ 9 ] However, the imbalance of autophagy of OP‐BMSCs leads to cell senescence, decline in number and function, resulting in insufficient osteogenic capacity. [ 10 ] Therefore, the regulatory role of autophagy in bone homeostasis indicates that autophagy may be a potential therapeutic target in the process of implant osseointegration.…”

Proteomics reveals the potential mechanism of Tanshinone IIA in promoting the Ex Vivo expansion of human bone marrow mesenchymal stem cells

“…For example, ZnCl2 was found to be used for extensive expansion of BMSCs in aged populations [ 19 ]. And, curcumin, the compounds from herbs, was reported to alleviate the senescence of BMSCs in vitro by activating the autophagy [ 20 ]. Moreover, it is found that A83-01, a small molecule inhibitor of transforming growth factor-β receptor, promoted proliferation of BMSCs [ 21 ].…”