Alteration of fatty acid oxidation by increased CPT1A on replicative senescence of placenta-derived mesenchymal stem cells

Abstract

BackgroundHuman placenta-derived mesenchymal stem cells (PD-MSCs) are powerful sources for cell therapy in regenerative medicine. However, a limited lifespan by senescence through mechanisms that are well unknown is the greatest obstacle. In the present study, we first demonstrated the characterization of replicative senescent PD-MSCs and their possible mitochondrial functional alterations.MethodsHuman PD-MSCs were cultured to senescent cells for a long period of time. The cells of before passage number 8 were early cells and after passage number 14 were late cells. Also, immortalized cells of PD-MSCs (overexpressed hTERT gene into PD-MSCs) after passage number 14 were positive control of non-senescent cells. The characterization and mitochondria analysis of PD-MSCs were explored with long-term cultivation.ResultsLong-term cultivation of PD-MSCs exhibited increases of senescent markers such as SA-β-gal and p21 including apoptotic factor, and decreases of proliferation, differentiation potential, and survival factor. Mitochondrial dysfunction was also observed in membrane potential and metabolic flexibility with enlarged mitochondrial mass. Interestingly, we founded that fatty acid oxidation (FAO) is an important metabolism in PD-MSCs, and carnitine palmitoyltransferase1A (CPT1A) overexpressed in senescent PD-MSCs. The inhibition of CPT1A induced a change of energy metabolism and reversed senescence of PD-MSCs.ConclusionsThese findings suggest that alteration of FAO by increased CPT1A plays an important role in mitochondrial dysfunction and senescence of PD-MSCs during long-term cultivation.

Functionally enhanced placenta-derived mesenchymal stem cells inhibit adipogenesis in orbital fibroblast with graves’ ophthalmopathy

“…1h). Previously, we confirmed in naïve MSCs as multi-differentiation potentials [19]. After differentiations, osteogenic-specific markers (Osteocalcin; OC and Collagen Type 1 alpha 1; COL1A1) and adipogenic-specific markers (Adipsin and peroxisome proliferator-activated receptor gamma; PPAR-γ) were expressed at high level in differentiated PD-MSCs PRL−1 by qRT-PCR (Fig.…”

Tri-Herbal Medicine Divya Sarva-Kalp-Kwath (Livogrit) Regulates Fatty Acid-Induced Steatosis in Human HepG2 Cells through Inhibition of Intracellular Triglycerides and Extracellular Glycerol Levels

“…Hepatic lipid metabolism is a complex process involving molecular events involving the roles of transcription factors, lipogenic, and fatty acid transporter genes [ 44 , 45 , 46 , 47 ]. Their modulation can lead to the development of steatosis along with reduced mitochondrial energy metabolism.…”

Lipid Players of Cellular Senescence

“…Seok et al found that CPT1 expression and fatty acid oxidation were increased in senescent human placenta-derived mesenchymal stem cells as compared to their proliferating counterparts, likely through the inactivation of ACC1 [ 78 ]. They also showed that mitochondrial dysfunction, the levels of reactive oxygen species, and senescence were reduced when CPT1 was inhibited [ 78 ], suggesting that CPT1 activity and fatty acid breakdown might play roles in maintaining mitochondrial function in senescence. Overall, these studies suggest the involvement of fatty acid and their metabolism in cellular senescence occur through a complex mechanism that seems to be dependent on tissue type and developmental stage.…”