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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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Histology of heart of MI model rats transplanted with young or old MSCs.The hearts of MI model rats were sectioned and stained with Masson's Trichrome 4 weeks after transplantation. Fibrosis and total left ventricle area were measured. The percentage of the fibrotic area was calculated as (fibrosis area/LV area) ×100%. N = 10 per group. * p<0.05 compared with PBS group; ** p<0.01 compared with PBS group; # p<0.05 compared with Old donor group; ## p<0.01 compared with Old donor group.
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pone-0111850-g005: Histology of heart of MI model rats transplanted with young or old MSCs.The hearts of MI model rats were sectioned and stained with Masson's Trichrome 4 weeks after transplantation. Fibrosis and total left ventricle area were measured. The percentage of the fibrotic area was calculated as (fibrosis area/LV area) ×100%. N = 10 per group. * p<0.05 compared with PBS group; ** p<0.01 compared with PBS group; # p<0.05 compared with Old donor group; ## p<0.01 compared with Old donor group.

Mentions: As the viability of young and old MSCs differed, will there be a significant difference in their potential in repairing infarcted myocardium? To answer that, 4 weeks after transplantation, the infarct size and wall thickness of hearts were measured. Compared with PBS control group, both transplantation of young and old MSCs reduced the infarct size and increased the wall thickness. However, when compared with young MSCs, significant defect of old MSCs was observed (Figure 5).


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)

Histology of heart of MI model rats transplanted with young or old MSCs.The hearts of MI model rats were sectioned and stained with Masson's Trichrome 4 weeks after transplantation. Fibrosis and total left ventricle area were measured. The percentage of the fibrotic area was calculated as (fibrosis area/LV area) ×100%. N = 10 per group. * p<0.05 compared with PBS group; ** p<0.01 compared with PBS group; # p<0.05 compared with Old donor group; ## p<0.01 compared with Old donor group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111850-g005: Histology of heart of MI model rats transplanted with young or old MSCs.The hearts of MI model rats were sectioned and stained with Masson's Trichrome 4 weeks after transplantation. Fibrosis and total left ventricle area were measured. The percentage of the fibrotic area was calculated as (fibrosis area/LV area) ×100%. N = 10 per group. * p<0.05 compared with PBS group; ** p<0.01 compared with PBS group; # p<0.05 compared with Old donor group; ## p<0.01 compared with Old donor group.
Mentions: As the viability of young and old MSCs differed, will there be a significant difference in their potential in repairing infarcted myocardium? To answer that, 4 weeks after transplantation, the infarct size and wall thickness of hearts were measured. Compared with PBS control group, both transplantation of young and old MSCs reduced the infarct size and increased the wall thickness. However, when compared with young MSCs, significant defect of old MSCs was observed (Figure 5).

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