Open AccessMelatonin protects ADSC s from ROS and enhances their therapeutic potency in a rat model of myocardial infarction
Author(s) -
Zhu Ping,
Liu Jianfeng,
Shi Jinxin,
Zhou Qian,
Liu Jie,
Zhang Xianwei,
Du Zhiyan,
Liu Qiaowei,
Guo Yuanyuan
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12610
Subject(s) - mesenchymal stem cell , melatonin , hepatocyte growth factor , pharmacology , cancer research , chemistry , medicine , biology , microbiology and biotechnology , endocrinology , receptor
Myocardial infarction ( MI ) is a major cause of death and disability worldwide. In the last decade, mesenchymal stem cells ( MSC s) based cell therapy has emerged as a promising therapeutic strategy. Although great advance have been made using MSC s to treat MI , the low viability of transplanted MSC s severely limits the efficiency of MSC s therapy. Here, we show evidence that ex vivo pre‐treatment with melatonin, an endogenous hormone with newly found anti‐oxidative activity, could improve survival and function of adipose tissue derived MSC s ( ADSC s) in vitro as well as in vivo . ADSC s with 5 μM melatonin pre‐treatment for 24 hrs showed increased expression of the antioxidant enzyme catalase and Cu/Zn superoxide dismutase ( SOD ‐1), as well as pro‐angiogenic and mitogenic factors like insulin‐like growth factor 1, basic fibroblast growth factor, hepatocyte growth factor (HGF), epidermal growth factor. Furthermore, melatonin pre‐treatment protected MSC s from reactive oxygen species ( ROS ) induced apoptosis both directly by promoting anti‐apoptosis kinases like p‐Akt as well as blocking caspase cascade, and indirectly by restoring the ROS impaired cell adhesion. Using a rat model of MI , we found that melatonin pre‐treatment enhanced the viability of engrafted ADSC s, and promoted their therapeutic potency. Hopefully, our results may shed light on the design of more effective therapeutic strategies treating MI by MSC s in clinic.