Title

Cell Membrane Damage Is Involved In The Impaired Survival Of Bone Marrow Stem Cells By Oxidized Low-Density Lipoprotein

Keywords

Cell survival; Membrane damage; Mesenchymal stem cells; MG53; Ox-LDL

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.

Publication Date

12-1-2014

Publication Title

Journal of Cellular and Molecular Medicine

Volume

18

Issue

12

Number of Pages

2445-2453

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1111/jcmm.12424

Socpus ID

84911427889 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84911427889

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