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Open Access Highly Accessed Research article

TGF-β1 induces senescence of bone marrow mesenchymal stem cells via increase of mitochondrial ROS production

Junfang Wu1, Jie Niu1, Xiaopeng Li2, Xianwei Wang1, Zhikun Guo1 and Fenxi Zhang3*

Author Affiliations

1 Key Laboratory of Henan Province for Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, China

2 The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, China

3 Department of Anatomy, Xinxiang Medical University, Xinxiang 453003, China

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BMC Developmental Biology 2014, 14:21  doi:10.1186/1471-213X-14-21

Published: 18 May 2014

Abstract

Background

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-β) is one of the most commonly used biological reagents for induction of cardiomyocyte differentiation of bmMSCs. Previous studies have shown that TGF-β induces senescence in several cell types. However, whether TGF-β affects senescence of bmMSCs has not been elucidated. The goal of this study was to investigate the effect of TGF-β1 on senescence of bmMSCs and the underlying mechanisms.

Results

We found that TGF-β1 increased activity of senescence-associated-galactosidase (SA-Gal) and production of mitochondrial reactive oxygen species (mtROS) in bmMSCs in a dose-dependent manner. TGF-β1 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-β1-induced mtROS production and SA-Gal activity.

Conclusion

TGF-β1 can induce senescence of bmMSCs, which at least partially depends on mtROS production.

Keywords:
Transforming growth factor beta 1; Bone marrow mesenchymal stem cells; Cell senescence; Senescence-associated-galactosidase activity; Mitochondrial reactive oxygen species