Aging increases the susceptivity of MSCs to reactive oxygen species and impairs their therapeutic potency for myocardial infarction.
Myocardial infarction (MI) is one of the leading causes of death worldwide and Mesenchymal Stem Cells (MSCs) transplantation has been considered a promising therapy. Recently, it was reported that the therapeutic effectiveness of MSCs is dependent on the age of the donor, yet the underlying mechanism has not been thoroughly investigated. This study was designed to investigate whether this impaired therapeutic potency is caused by an increased susceptivity of MSCs from old donors to reactive oxygen species (ROS). The MSCs were isolated from the subcutaneous inguinal region of young (8-10 weeks) and old (18 months) Sprague-Dawley (SD) rats. By exposing these MSCs to H2O2, we found that the adhesion of MSCs from old donors was damaged more severely. Specifically, decreased expression of integrin and reduced phosphorylation of focal adhesion kinase Src and FAK were observed. Furthemore, H2O2 triggered an increased apoptosis of MSCs from old donors. To study the viability and therapeutic potency of MSCs from young and old donors in vivo, these MSCs were transplanted into acute MI model rats. We observed a more rapidly decreased survival rate of the old MSCs in the infarct region, which may be caused by their increased susceptivity to the micro-environmental ROS, as transplantation of the old MSCs with N-acetyl-L-cysteine (NAC), a ROS scavenger, protected them. The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart. Our study may help to understand the mechanism of MSCs-host interaction during MI, as well as shed light on the design of therapeutic strategy in clinic.
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Liang
L
Li
Department of Emergency, First hospital affiliated to general hospital of People's Liberation Army, Beijing, China.
Yingfei
Y
Guo
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Hongxia
H
Zhai
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Yaxin
Y
Yin
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Jinjin
J
Zhang
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Haiwei
H
Chen
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Lei
L
Wang
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Na
N
Li
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Runmei
R
Liu
First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.
Yunfeng
Y
Xia
D000111:Acetylcysteine / Q000627:therapeutic use; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000633:toxicity; D016023:Integrins / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000633:toxicity*
D016166:Free Radical Scavengers; D016023:Integrins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000111:Acetylcysteine