Edaravone promotes activation of resident cardiac stem cells by transplanted mesenchymal stem cells in a rat myocardial infarction model

Abstract Objective To explore the effect of edaravone (ED) on BMSCs transplanted to treat acute myocardial infarction (AMI) and the underlying mechanism. Methods After pretreated or treated by ED under a deep hypoxia and serum deprivation (DH/SD) condition, the rat BMSCs were evaluated for reactive...

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Bibliographic Details
Published in:The Journal of thoracic and cardiovascular surgery 2016-08, Vol.152 (2), p.570-582
Main Authors: Zhang, Guang-Wei, MD, Gu, Tian-Xiang, MD, Sun, Xue-Jun, Wang, Chunyue, MD, Qi, Xun, MD, Wang, Xiao-Bing, MD, Li-Ling, Jesse, MD, PhD
Format: Article
Language:English
Subjects:
Animals
Antipyrine - analogs & derivatives
Antipyrine - pharmacology
Apoptosis - drug effects
Cardiothoracic Surgery
Cell Movement - drug effects
Cells, Cultured
Cytokines - metabolism
Disease Models, Animal
edaravone
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - metabolism
myocardial infarction
Myocardial Infarction - metabolism
Myocardial Infarction - pathology
Myocardial Infarction - physiopathology
Myocardial Infarction - surgery
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Neovascularization, Physiologic - drug effects
Paracrine Communication - drug effects
Proto-Oncogene Proteins c-akt - metabolism
Rats, Sprague-Dawley
Reactive Oxygen Species - metabolism
Recovery of Function
regeneration
Regeneration - drug effects
Signal Transduction - drug effects
stem cell transplantation
Stem Cells - metabolism
Stem Cells - pathology
Time Factors
ventricular function
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Summary:Abstract Objective To explore the effect of edaravone (ED) on BMSCs transplanted to treat acute myocardial infarction (AMI) and the underlying mechanism. Methods After pretreated or treated by ED under a deep hypoxia and serum deprivation (DH/SD) condition, the rat BMSCs were evaluated for reactive oxygen species (ROS), Akt pathway, apoptosis, migration, and paracrine function mediating cardiac stem cells (CSCs) activation. ED pretreated BMSCs, control-released ED and BMSCs were respectively transplanted into a rat AMI model. Apoptosis and paracrine functions of the BMSCs, resident CSCs activation, and myocardial regeneration and function were measured at various time points. Results Compared with the control and ED-pretreatment, ED-treatment showed significantly promoted apoptosis inhibition, migration and cytokine secretion of BMSCs under an in vitro DH/SD condition ( P < 0.05), via inhibiting intracellular accumulation of ROS and prolonging the Akt pathway activation. 24 hrs post-operatively, up-regulated expression of cytokines within the transplanted area and decreased apoptotic BMSCs were detected in the BMSCs+ED group compared with the BMSCs and EDpreBMSCs groups (n=10 each group, P < 0.05). 4 weeks later, the BMSCs+ED group showed more CSCs, CSCs-derived cardiomyocytes, new vessels and myocardial density within the ischemic area, additionally improved ejection fraction compared with the other groups (n=10 each group, P < 0.05). Conclusion ED can protect the BMSCs against hypoxia and activate their potential to activate CSCs via the Akt pathway. The combined treatment can promote angiogenesis, resident CSCs-mediated myocardial regeneration and cardiac function following AMI, providing a new strategy for cell therapy.
ISSN:0022-5223
1097-685X
DOI:10.1016/j.jtcvs.2016.02.071