title: Edaravone promotes activation of resident cardiac stem cells by transplanted mesenchymal stem cells in a rat myocardial infarction model.
abstract: To explore the effect of edaravone on bone marrow mesenchymal stem cells (BMSCs) transplanted to treat acute myocardial infarction (AMI) and the underlying mechanism.
  
  
  
  After pretreatment or treatment with edaravone under conditions of deep hypoxia and serum deprivation, the rat BMSCs were evaluated for reactive oxygen species (ROS), Akt pathway, apoptosis, migration, and paracrine function mediating cardiac stem cell (CSC) activation. Edaravone-pretreated BMSCs, control-released edaravone, and BMSCs were respectively transplanted into a rat AMI model. Apoptosis and paracrine functions of the BMSCs, resident CSC activation, and myocardial regeneration and function were measured at various time points.
  
  
  
  Compared with the control and edaravone pretreatment, edaravone treatment showed significantly increased apoptosis inhibition, migration, and cytokine secretion of BMSCs under an in vitro deep hypoxia and serum deprivation condition (P < .05), via inhibiting intracellular accumulation of ROS and prolonging the Akt pathway activation. At 24 hours postoperatively, up-regulated expression of cytokines within the transplanted area, and decreased apoptotic BMSCs, were detected in the BMSC + edaravone group, compared with the BMSCs and edaravone pretreatment BMSC groups (n = 10 for each group, P < .05). Four weeks later, the BMSCs + edaravone group showed more CSCs, CSC-derived cardiomyocytes, new vessels, and myocardial density within the ischemic area, and improved ejection fraction, compared with the other groups (n = 10 in each group, P < .05).
  
  
  
  Edaravone can protect the BMSCs against hypoxia and activate their potential to activate CSCs via the Akt pathway. The combined treatment can promote angiogenesis, resident CSC-mediated myocardial regeneration, and cardiac function after AMI, providing a new strategy for cell therapy.
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, China. Electronic address: cmugtx@sina.com.
authors.forename: Tian-Xiang
authors.initials: TX
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China; Department of Anesthesiology of the First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Cardiovascular Institute, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, China.
authors.forename: Chunyue
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Radiology, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Echocardiography, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.affiliation: Institute of Genetic Medicine, School of Life Science, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China.
authors.forename: Jesse
authors.initials: J
authors.lastname: Li-Ling
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D000077553:Edaravone; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020127:Recovery of Function; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D000077553:Edaravone; D000983:Antipyrine
keywords: edaravone; myocardial infarction; regeneration; stem cell transplantation; ventricular function