title: Cell membrane damage is involved in the impaired survival of bone marrow stem cells by oxidized low-density lipoprotein.
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.
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.forename: Chandrakala A
authors.initials: CA
authors.lastname: Narasimhulu
authors.forename: Hong
authors.initials: H
authors.lastname: Hao
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.forename: Guanglong
authors.initials: G
authors.lastname: He
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Minxiang
authors.initials: M
authors.lastname: Lei
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism / Q000493:pharmacokinetics; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D018613:Microscopy, Confocal; D039902:Multipotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; C073804:FM1 43; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C558399:TRIM72 protein, human; D000070584:Tripartite Motif Proteins; C099252:oxidized low density lipoprotein; D000111:Acetylcysteine
keywords: MG53; cell survival; membrane damage; mesenchymal stem cells; ox-LDL