Bone marrow derived mesenchymal stem cells (bmMSCs) are multipotent cells that can differentiate into diverse cell types, including cardiomyocytes. BmMSC-based transplantation is capable of repairing acute and chronic myocardial infarction.
Prior to the transplantation, MSCs are usually induced in vitro by biological reagents and chemicals for directional differentiation. Transforming growth factor beta (TGF-beta) is one of the most commonly used biological reagents for induction of cardiomyocyte differentiation of bmMSCs.
Previous studies have shown that TGF-beta induces senescence in several cell types. However, whether TGF-beta affects senescence of bmMSCs has not been elucidated.
The goal of this study was to investigate the effect of TGF-beta1 on senescence of bmMSCs and the underlying mechanisms.
Results:
We found that TGF-beta1 increased activity of senescence-associated-galactosidase (SA-Gal) and production of mitochondrial reactive oxygen species (mtROS) in bmMSCs in a dose-dependent manner. TGF-beta1 also significantly decreased expression of superoxide dismutase 2 (SOD2) and Id1, and increased expression of 4-Hydroxynonenal (4-HNE) subunits and p16 in bmMSCs in a dose-dependent manner.
Pre-treatment with mtROS inhibitor acetyl-L-carnitine (ALCAR, 0.1 mM) significantly inhibited TGF-beta1-induced mtROS production and SA-Gal activity.
Conclusion:
TGF-beta1 can induce senescence of bmMSCs, which at least partially depends on mtROS production.
Author: Junfang WuJie NiuXiaopeng LiXianwei WangZhikun GuoFenxi Zhang
Credits/Source: BMC Developmental Biology 2014, 14:21
Published on: 2014-05-18
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