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CD34+ cells represent highly functional endothelial progenitor cells in murine bone marrow.

Yang J, Ii M, Kamei N, Alev C, Kwon SM, Kawamoto A, Akimaru H, Masuda H, Sawa Y, Asahara T - PLoS ONE (2011)

Bottom Line: Although CD34(+) cells showed the lowest EPC colony forming activity, CD34(+) cells exhibited under endothelial culture conditions a more adherent phenotype compared with the others, demonstrating the highest mRNA expression levels of endothelial markers vWF, VE-cadherin, and Flk-1.Furthermore, a dramatic increase in immediate recruitment of cells to the myocardium following myocardial infarction and systemic cell injection was observed for CD34(+) cells comparing with others, which could be explained by the highest mRNA expression levels of key homing-related molecules Integrin β2 and CXCR4 in CD34(+) cells.Cell retention and incorporation into the vasculature of the ischemic myocardium was also markedly increased in the CD34(+) cell-injected group, giving a possible explanation for significant reduction in fibrosis area, significant increase in neovascularization and the best cardiac functional recovery in this group in comparison with the others.

View Article: PubMed Central - PubMed

Affiliation: Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, Kobe, Japan.

ABSTRACT

Background: Endothelial progenitor cells (EPCs) were shown to have angiogenic potential contributing to neovascularization. However, a clear definition of mouse EPCs by cell surface markers still remains elusive. We hypothesized that CD34 could be used for identification and isolation of functional EPCs from mouse bone marrow.

Methodology/principal findings: CD34(+) cells, c-Kit(+)/Sca-1(+)/Lin(-) (KSL) cells, c-Kit(+)/Lin(-) (KL) cells and Sca-1(+)/Lin(-) (SL) cells were isolated from mouse bone marrow mononuclear cells (BMMNCs) using fluorescent activated cell sorting. EPC colony forming capacity and differentiation capacity into endothelial lineage were examined in the cells. Although CD34(+) cells showed the lowest EPC colony forming activity, CD34(+) cells exhibited under endothelial culture conditions a more adherent phenotype compared with the others, demonstrating the highest mRNA expression levels of endothelial markers vWF, VE-cadherin, and Flk-1. Furthermore, a dramatic increase in immediate recruitment of cells to the myocardium following myocardial infarction and systemic cell injection was observed for CD34(+) cells comparing with others, which could be explained by the highest mRNA expression levels of key homing-related molecules Integrin β2 and CXCR4 in CD34(+) cells. Cell retention and incorporation into the vasculature of the ischemic myocardium was also markedly increased in the CD34(+) cell-injected group, giving a possible explanation for significant reduction in fibrosis area, significant increase in neovascularization and the best cardiac functional recovery in this group in comparison with the others.

Conclusion: These findings suggest that mouse CD34(+) cells may represent a functional EPC population in bone marrow, which could benefit the investigation of therapeutic EPC biology.

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Functional analysis of treated hearts by echocardiography.Echocardiographic parameters for cardiac function 28 days vs. 7 days after myocardial infarction and treatments. The following parameters: left ventricular end diastolic diameter (LVEDD) (a), left ventricular end systolic diameter (LVESD) (b), left ventricular ejection fraction (EF) (c) and left ventricular fractional shortening (FS) (d) were measured in the PBS-, the KSL-, the KL-, the SL- and the CD34+ cell-injected groups, and change of each parameter between day 7 and day 28 after surgery was calculated and averaged (n = 3).
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pone-0020219-g010: Functional analysis of treated hearts by echocardiography.Echocardiographic parameters for cardiac function 28 days vs. 7 days after myocardial infarction and treatments. The following parameters: left ventricular end diastolic diameter (LVEDD) (a), left ventricular end systolic diameter (LVESD) (b), left ventricular ejection fraction (EF) (c) and left ventricular fractional shortening (FS) (d) were measured in the PBS-, the KSL-, the KL-, the SL- and the CD34+ cell-injected groups, and change of each parameter between day 7 and day 28 after surgery was calculated and averaged (n = 3).

Mentions: There were no significant differences in preoperative echocardiographic parameters, LVEDD (left ventricular end-diastolic dimension), LVESD (left ventricular end-systolic dimension), EF (ejection fraction) and FS (fractional shortening) among any groups. Echocardiography performed 7 days and 28 days after cell transplantation demonstrated that ΔLVEDD (day 28-day 7) was significantly smaller in the CD34+ cell-treated group than in the PBS-, the KSL- and the SL-treated groups (P<0.05 vs PBS, KSL and SL) (Figure 10a). The ΔLVEDD was also significantly smaller in the KL-treated group than in the PBS- and the KSL-treated groups (P<0.05) (Figure 10a). However, ΔLVEDD was similar in the PBS-, the KSL- and the SL-treated groups (Figure 10a). The ΔLVESD (day 28-day 7) was significantly smaller in the CD34+ cell-treated group than in the PBS-, the KSL- and the SL-treated groups (P<0.05 vs PBS, KSL and SL) (Figure 10b). The ΔEF (day 28-day 7) was significantly greater in the CD34+ cell-treated group than in the PBS-, the KSL- and the SL-treated groups (P<0.05 vs PBS, KSL and SL) (Figure 10c). The ΔEF was also significantly smaller in the PBS-treated group than in the KSL-, the KL- and the SL-treated groups (P<0.05) (Figure 10c). The ΔFS (day 28-day 7) was significantly greater in the CD34+ cell-treated group than in the PBS-, the KSL-, the KL- and the SL-treated groups (P<0.05 vs PBS, KSL, KL and SL) (Figure 10d). The ΔFS was also significantly smaller in the PBS-treated group than in the KSL-, the KL- and the SL-treated groups (P<0.05) (Figure 10d). Overall, transplantation of CD34+ cells exhibited significant LV functional recovery among all cell-transplanted groups following MI, which is consistent with the results of histological analysis.


CD34+ cells represent highly functional endothelial progenitor cells in murine bone marrow.

Yang J, Ii M, Kamei N, Alev C, Kwon SM, Kawamoto A, Akimaru H, Masuda H, Sawa Y, Asahara T - PLoS ONE (2011)

Functional analysis of treated hearts by echocardiography.Echocardiographic parameters for cardiac function 28 days vs. 7 days after myocardial infarction and treatments. The following parameters: left ventricular end diastolic diameter (LVEDD) (a), left ventricular end systolic diameter (LVESD) (b), left ventricular ejection fraction (EF) (c) and left ventricular fractional shortening (FS) (d) were measured in the PBS-, the KSL-, the KL-, the SL- and the CD34+ cell-injected groups, and change of each parameter between day 7 and day 28 after surgery was calculated and averaged (n = 3).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105013&req=5

pone-0020219-g010: Functional analysis of treated hearts by echocardiography.Echocardiographic parameters for cardiac function 28 days vs. 7 days after myocardial infarction and treatments. The following parameters: left ventricular end diastolic diameter (LVEDD) (a), left ventricular end systolic diameter (LVESD) (b), left ventricular ejection fraction (EF) (c) and left ventricular fractional shortening (FS) (d) were measured in the PBS-, the KSL-, the KL-, the SL- and the CD34+ cell-injected groups, and change of each parameter between day 7 and day 28 after surgery was calculated and averaged (n = 3).
Mentions: There were no significant differences in preoperative echocardiographic parameters, LVEDD (left ventricular end-diastolic dimension), LVESD (left ventricular end-systolic dimension), EF (ejection fraction) and FS (fractional shortening) among any groups. Echocardiography performed 7 days and 28 days after cell transplantation demonstrated that ΔLVEDD (day 28-day 7) was significantly smaller in the CD34+ cell-treated group than in the PBS-, the KSL- and the SL-treated groups (P<0.05 vs PBS, KSL and SL) (Figure 10a). The ΔLVEDD was also significantly smaller in the KL-treated group than in the PBS- and the KSL-treated groups (P<0.05) (Figure 10a). However, ΔLVEDD was similar in the PBS-, the KSL- and the SL-treated groups (Figure 10a). The ΔLVESD (day 28-day 7) was significantly smaller in the CD34+ cell-treated group than in the PBS-, the KSL- and the SL-treated groups (P<0.05 vs PBS, KSL and SL) (Figure 10b). The ΔEF (day 28-day 7) was significantly greater in the CD34+ cell-treated group than in the PBS-, the KSL- and the SL-treated groups (P<0.05 vs PBS, KSL and SL) (Figure 10c). The ΔEF was also significantly smaller in the PBS-treated group than in the KSL-, the KL- and the SL-treated groups (P<0.05) (Figure 10c). The ΔFS (day 28-day 7) was significantly greater in the CD34+ cell-treated group than in the PBS-, the KSL-, the KL- and the SL-treated groups (P<0.05 vs PBS, KSL, KL and SL) (Figure 10d). The ΔFS was also significantly smaller in the PBS-treated group than in the KSL-, the KL- and the SL-treated groups (P<0.05) (Figure 10d). Overall, transplantation of CD34+ cells exhibited significant LV functional recovery among all cell-transplanted groups following MI, which is consistent with the results of histological analysis.

Bottom Line: Although CD34(+) cells showed the lowest EPC colony forming activity, CD34(+) cells exhibited under endothelial culture conditions a more adherent phenotype compared with the others, demonstrating the highest mRNA expression levels of endothelial markers vWF, VE-cadherin, and Flk-1.Furthermore, a dramatic increase in immediate recruitment of cells to the myocardium following myocardial infarction and systemic cell injection was observed for CD34(+) cells comparing with others, which could be explained by the highest mRNA expression levels of key homing-related molecules Integrin β2 and CXCR4 in CD34(+) cells.Cell retention and incorporation into the vasculature of the ischemic myocardium was also markedly increased in the CD34(+) cell-injected group, giving a possible explanation for significant reduction in fibrosis area, significant increase in neovascularization and the best cardiac functional recovery in this group in comparison with the others.

View Article: PubMed Central - PubMed

Affiliation: Group of Vascular Regeneration Research, Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, Kobe, Japan.

ABSTRACT

Background: Endothelial progenitor cells (EPCs) were shown to have angiogenic potential contributing to neovascularization. However, a clear definition of mouse EPCs by cell surface markers still remains elusive. We hypothesized that CD34 could be used for identification and isolation of functional EPCs from mouse bone marrow.

Methodology/principal findings: CD34(+) cells, c-Kit(+)/Sca-1(+)/Lin(-) (KSL) cells, c-Kit(+)/Lin(-) (KL) cells and Sca-1(+)/Lin(-) (SL) cells were isolated from mouse bone marrow mononuclear cells (BMMNCs) using fluorescent activated cell sorting. EPC colony forming capacity and differentiation capacity into endothelial lineage were examined in the cells. Although CD34(+) cells showed the lowest EPC colony forming activity, CD34(+) cells exhibited under endothelial culture conditions a more adherent phenotype compared with the others, demonstrating the highest mRNA expression levels of endothelial markers vWF, VE-cadherin, and Flk-1. Furthermore, a dramatic increase in immediate recruitment of cells to the myocardium following myocardial infarction and systemic cell injection was observed for CD34(+) cells comparing with others, which could be explained by the highest mRNA expression levels of key homing-related molecules Integrin β2 and CXCR4 in CD34(+) cells. Cell retention and incorporation into the vasculature of the ischemic myocardium was also markedly increased in the CD34(+) cell-injected group, giving a possible explanation for significant reduction in fibrosis area, significant increase in neovascularization and the best cardiac functional recovery in this group in comparison with the others.

Conclusion: These findings suggest that mouse CD34(+) cells may represent a functional EPC population in bone marrow, which could benefit the investigation of therapeutic EPC biology.

Show MeSH
Related in: MedlinePlus