Cell membrane damage is involved in the impaired survival of bone marrow stem cells by oxidized low-density lipoprotein
Abbreviated Journal Title
J. Disp. Technol.
mesenchymal stem cells; ox-LDL; MG53; membrane damage; cell survival; ENDOTHELIAL PROGENITOR CELLS; SMOOTH-MUSCLE-CELLS; NEONATAL RAT; CARDIOMYOCYTES; OX-LDL; MYOCARDIAL-INFARCTION; 3-KINASE/AKT PATHWAY; MUSCULAR-DYSTROPHY; INDUCED APOPTOSIS; S-NITROSYLATION; PROTEIN-KINASE; Cell Biology; Medicine, Research & Experimental
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.
X. Li; Y. Xiao; Y. Q. Cui; T. Tan; C. A. Narasimhulu; H. Hao; L. J. Liu; J. Zhang; G. L. He; C. M. Verfaillie; M. X. Lei; S. Parthasarathy; J. J. Ma; H. Zhu;Z. G. Liu
"Cell membrane damage is involved in the impaired survival of bone marrow stem cells by oxidized low-density lipoprotein" (2014). Faculty Bibliography 2010s. 5694.