Cell membrane damage is involved in the impaired survival of bone marrow stem cells by oxidized low‐density lipoprotein

Journal of Cellular and Molecular Medicine

Xin Li²  Yuan Xiao³  Yuqi Cui³  Tao Tan⁵  Chandrakala A. Narasimhulu¹  Hong Hao³  Lingjuan Liu³  Jia Zhang³  Guanglong He³  Catherine M. Verfaillie⁴  Minxiang Lei²  Sampath Parthasarathy¹  Jianjie Ma⁵  Hua Zhu⁵ 

[1] Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA;Xiangya Hospital of Central South University, Changsha, Hunan, China;Davis Heart & Lung Research Institute and Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA;Stem Cell Institute, University of Leuven, Leuven, Belgium;Davis Heart & Lung Research Institute, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

关键词: mesenchymal stem cells;    ox‐LDL;    MG53;    membrane damage;    cell survival;   

DOI  :  10.1111/jcmm.12424

来源: Wiley

【 摘 要 】

Abstract

Cell therapy with bone marrow stem cells (BMSCs) remains a viable option for tissue repair and regeneration. A major challenge for cell therapy is the limited cell survival after implantation. This study was to investigate the effect of oxidized low-density lipoprotein (ox-LDL, naturally present in human blood) on BMSC injury and the effect of MG53, a tissue repair protein, for the improvement of stem cell survival. Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox-LDL, which caused significant cell death as reflected by the increased LDH release to the media. Exposure of MAPCs to ox-LDL led to entry of fluorescent dye FM1-43 measured under confocal microscope, suggesting damage to the plasma membrane. Ox-LDL also generated reactive oxygen species (ROS) as measured with electron paramagnetic resonance spectroscopy. While antioxidant N-acetylcysteine completely blocked ROS production from ox-LDL, it failed to prevent ox-LDL-induced cell death. When MAPCs were treated with the recombinant human MG53 protein (rhMG53) ox-LDL induced LDH release and FM1-43 dye entry were significantly reduced. In the presence of rhMG53, the MAPCs showed enhanced cell survival and proliferation. Our data suggest that membrane damage induced by ox-LDL contributed to the impaired survival of MAPCs. rhMG53 treatment protected MAPCs against membrane damage and enhanced their survival which might represent a novel means for improving efficacy for stem cell-based therapy for treatment of diseases, especially in setting of hyperlipidemia.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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