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Aging increases the susceptivity of MSCs to reactive oxygen species and impairs their therapeutic potency for myocardial infarction.

Li L, Guo Y, Zhai H, Yin Y, Zhang J, Chen H, Wang L, Li N, Liu R, Xia Y - PLoS ONE (2014)

Bottom Line: 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.The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart.

View Article: PubMed Central - PubMed

Affiliation: First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.

ABSTRACT
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.

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Apoptosis of MSCs from young and old donors induced by ROS.MSCs from young and old donors were treated by 0, 25, 50 or 100 µM H2O2 for 24 h. Then Flow cytometry analysis was performed to detect cell apoptosis using Anexin V apoptosis kit. ** p<0.01
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pone-0111850-g003: Apoptosis of MSCs from young and old donors induced by ROS.MSCs from young and old donors were treated by 0, 25, 50 or 100 µM H2O2 for 24 h. Then Flow cytometry analysis was performed to detect cell apoptosis using Anexin V apoptosis kit. ** p<0.01

Mentions: We next examined the viability of young and old MSCs in ROS environment. As shown in Figure 3, the apoptosis of MSCs were triggered at an H2O2 concentration of 25 µM and gradually increased in a dose-dependent manner. A two-fold increase in apoptosis of old MSCs was observed compared with that of the young MSCs at a same H2O2 concentration. Together, these in vitro data suggest that MSCs from old donors are more susceptible to exogenous ROS induced adhesion impairment and apoptosis than the ones from young donors.


Aging increases the susceptivity of MSCs to reactive oxygen species and impairs their therapeutic potency for myocardial infarction.

Li L, Guo Y, Zhai H, Yin Y, Zhang J, Chen H, Wang L, Li N, Liu R, Xia Y - PLoS ONE (2014)

Apoptosis of MSCs from young and old donors induced by ROS.MSCs from young and old donors were treated by 0, 25, 50 or 100 µM H2O2 for 24 h. Then Flow cytometry analysis was performed to detect cell apoptosis using Anexin V apoptosis kit. ** p<0.01
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230939&req=5

pone-0111850-g003: Apoptosis of MSCs from young and old donors induced by ROS.MSCs from young and old donors were treated by 0, 25, 50 or 100 µM H2O2 for 24 h. Then Flow cytometry analysis was performed to detect cell apoptosis using Anexin V apoptosis kit. ** p<0.01
Mentions: We next examined the viability of young and old MSCs in ROS environment. As shown in Figure 3, the apoptosis of MSCs were triggered at an H2O2 concentration of 25 µM and gradually increased in a dose-dependent manner. A two-fold increase in apoptosis of old MSCs was observed compared with that of the young MSCs at a same H2O2 concentration. Together, these in vitro data suggest that MSCs from old donors are more susceptible to exogenous ROS induced adhesion impairment and apoptosis than the ones from young donors.

Bottom Line: 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.The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart.

View Article: PubMed Central - PubMed

Affiliation: First Department of Cadres, First Hospital Affiliated to General Hospital of People's Liberation Army, Beijing, China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus