Limits...
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.

Show MeSH

Related in: MedlinePlus

Characterization of MSCs from young and old donors.A. Flow cytometry analysis of cultured MSCs. Both MSCs from young and old donor were positive for CD90, CD29 and negative for haematopoietic markers CD45FITC and CD34PE. B. Morphology and multiplex differentiation potential of cultured MSCs. The presence of adipocytes was verified by staining for triglycerides (red) with Oil Red O and the presence of active osteoblasts were verified by staining for calcium deposition (red) with Alizarin Red S. Representative images were shown. Scale bar: 100 µm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4230939&req=5

pone-0111850-g001: Characterization of MSCs from young and old donors.A. Flow cytometry analysis of cultured MSCs. Both MSCs from young and old donor were positive for CD90, CD29 and negative for haematopoietic markers CD45FITC and CD34PE. B. Morphology and multiplex differentiation potential of cultured MSCs. The presence of adipocytes was verified by staining for triglycerides (red) with Oil Red O and the presence of active osteoblasts were verified by staining for calcium deposition (red) with Alizarin Red S. Representative images were shown. Scale bar: 100 µm.

Mentions: Mesenchymal stem cells isolated from young and old donor rats were first characterized using flow cytometry for their expression of MSCs markers. As shown in Figure 1A, most of the young and old MSCs we isolated were positive for CD90 and CD29 expression (>99%), and negative for haematopoietic markers CD34 and CD45. For further confirmation, the MSCs were examined for their multiplex differentiation potential. By changing of culture conditions, these MSCs could differentiate into adipocytes and osteogenic cells, respectively (Figure 1B). No significant differences, neither in MSCs markers' expression nor in differentiation potential, were found between MSCs from young and old 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)

Characterization of MSCs from young and old donors.A. Flow cytometry analysis of cultured MSCs. Both MSCs from young and old donor were positive for CD90, CD29 and negative for haematopoietic markers CD45FITC and CD34PE. B. Morphology and multiplex differentiation potential of cultured MSCs. The presence of adipocytes was verified by staining for triglycerides (red) with Oil Red O and the presence of active osteoblasts were verified by staining for calcium deposition (red) with Alizarin Red S. Representative images were shown. Scale bar: 100 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111850-g001: Characterization of MSCs from young and old donors.A. Flow cytometry analysis of cultured MSCs. Both MSCs from young and old donor were positive for CD90, CD29 and negative for haematopoietic markers CD45FITC and CD34PE. B. Morphology and multiplex differentiation potential of cultured MSCs. The presence of adipocytes was verified by staining for triglycerides (red) with Oil Red O and the presence of active osteoblasts were verified by staining for calcium deposition (red) with Alizarin Red S. Representative images were shown. Scale bar: 100 µm.
Mentions: Mesenchymal stem cells isolated from young and old donor rats were first characterized using flow cytometry for their expression of MSCs markers. As shown in Figure 1A, most of the young and old MSCs we isolated were positive for CD90 and CD29 expression (>99%), and negative for haematopoietic markers CD34 and CD45. For further confirmation, the MSCs were examined for their multiplex differentiation potential. By changing of culture conditions, these MSCs could differentiate into adipocytes and osteogenic cells, respectively (Figure 1B). No significant differences, neither in MSCs markers' expression nor in differentiation potential, were found between MSCs from young and old 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