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.
Highlights
Cell therapy with stem cells remains a viable option for tissue repair and regeneration [1,2,3]
Rat multipotent adult progenitor cells (MAPCs) were seeded in a 24-well plate at a density of 1 9 104 cells/cm2 in the presence of Oxidized-low-density lipoprotein (ox-LDL) for up to 48 hrs with or without recombinant human MG53 protein (rhMG53)
We demonstrated that ox-LDL inhibited proliferation, induced apoptosis of Bone marrow-derived mesenchymal stem cells (BMSCs), and attenuated their endothelial differentiation [28, 29]
Summary
Cell therapy with stem cells remains a viable option for tissue repair and regeneration [1,2,3]. Bone marrow-derived mesenchymal stem cells (BMSCs) are an attractive source for cell therapy a 2014 The Authors. Been considered to cause the poor survival of transplanted cells, such as inflammation and hypoxia, the exact mechanism(s) remains largely unknown. Ox-LDL exhibits significant effects on progenitor cell especially endothelial progenitor cell (EPC) including apoptosis induction and suppression of function and therapeutic potential [18,19,20,21,22,23,24,25,26]. The cytokines produced by macrophage, leucocyte and platelet could indirectly modify the function of stem cells in the presence of ox-LDL [27]
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