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Effects of bone marrow mesenchymal stem cells (BM-MSCs) on rat pial microvascular remodeling after transient middle cerebral artery occlusion.

Lapi D, Vagnani S, Sapio D, Mastantuono T, Boscia F, Pignataro G, Penna C, Pagliaro P, Colantuoni A - Front Cell Neurosci (2015)

Bottom Line: This study was aimed to assess the effects of bone marrow mesenchymal stem cells (BM-MSCs) infused after MCAO on rat pial microcirculation.In conclusion, transient MCAO induced pial vascular remodeling characterized by arteriolar anastomotic arcades (originated from preexistent arterioles in penumbra area) able to overlap the ischemic core supplying blood to the neuronal tissue.BM-MSCs appear to accelerate angiogenic processes facilitating new vessel formation; this mechanism was promoted by an increase in VEGF and eNOS expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Medicine and Surgery, "Federico II" University Medical School Naples, Italy.

ABSTRACT
Previous studies have shown that the pial microcirculation remodeling improves neurological outcome after middle cerebral artery occlusion (MCAO), accompanied by higher expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), modulating in vivo angiogenesis. This study was aimed to assess the effects of bone marrow mesenchymal stem cells (BM-MSCs) infused after MCAO on rat pial microcirculation. Animals were subjected to 2 h MCAO followed by BM-MSCs infusion into internal carotid artery. Pial microcirculation was observed at different reperfusion times by fluorescence microscopy. Geometric characteristics of arteriolar networks, permeability increase, leukocyte adhesion, perfused capillary density, VEGF, and endothelial nitric oxide synthase (e-NOS) expression were evaluated. Green fluorescent protein (GFP)-BM-MSCs were used to evaluate their distribution and cell phenotype development during reperfusion. BM-MSCs stimulated a geometric rearrangement of pial networks with formation of new anastomotic vessels sprouting from preexistent arterioles in the penumbra at 7-14-28 days of reperfusion. At the same time VEGF and eNOS expression increased. GFP-BM-MSCs appear to be involved in endothelial and smooth muscle cell programming in the infarcted area. In conclusion, transient MCAO induced pial vascular remodeling characterized by arteriolar anastomotic arcades (originated from preexistent arterioles in penumbra area) able to overlap the ischemic core supplying blood to the neuronal tissue. BM-MSCs appear to accelerate angiogenic processes facilitating new vessel formation; this mechanism was promoted by an increase in VEGF and eNOS expression.

No MeSH data available.


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Colocalization of CD31 (A) and GFP-signal (B) in the infarcted region of a rat infused with GFP-BM-MSCs after 2h MCAO and observed after 7 days of reperfusion (I-GFP-MSCs-7R group). Control cells (C), merged (D).
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Figure 5: Colocalization of CD31 (A) and GFP-signal (B) in the infarcted region of a rat infused with GFP-BM-MSCs after 2h MCAO and observed after 7 days of reperfusion (I-GFP-MSCs-7R group). Control cells (C), merged (D).

Mentions: In particular, confocal analysis detected most of the GFP-BM-MSCs in close association with vessels at 7 days after infusion in ischemic animals (Figures 5, 6). To investigate the cells phenotype of transplanted GFP-BM-MSCs observed along vessels of the infarcted region, we performed immunofluorescence experiments with selective endothelial (Figure 5) or smooth muscle (Figure 5) cells markers. We observed higher coexpression of GFP signal with CD31 or vWF immunoreactivity, when compared to the cells coexpressing both GFP signal and α-SMA labeling. The ratio was 4:1 between CD31 or vWF and α-SMA. Our results indicate that most of the GFP-BM-MSCs appear to express mainly CD31 or vWF (data not shown) in the infarcted area (Figure 5).


Effects of bone marrow mesenchymal stem cells (BM-MSCs) on rat pial microvascular remodeling after transient middle cerebral artery occlusion.

Lapi D, Vagnani S, Sapio D, Mastantuono T, Boscia F, Pignataro G, Penna C, Pagliaro P, Colantuoni A - Front Cell Neurosci (2015)

Colocalization of CD31 (A) and GFP-signal (B) in the infarcted region of a rat infused with GFP-BM-MSCs after 2h MCAO and observed after 7 days of reperfusion (I-GFP-MSCs-7R group). Control cells (C), merged (D).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548191&req=5

Figure 5: Colocalization of CD31 (A) and GFP-signal (B) in the infarcted region of a rat infused with GFP-BM-MSCs after 2h MCAO and observed after 7 days of reperfusion (I-GFP-MSCs-7R group). Control cells (C), merged (D).
Mentions: In particular, confocal analysis detected most of the GFP-BM-MSCs in close association with vessels at 7 days after infusion in ischemic animals (Figures 5, 6). To investigate the cells phenotype of transplanted GFP-BM-MSCs observed along vessels of the infarcted region, we performed immunofluorescence experiments with selective endothelial (Figure 5) or smooth muscle (Figure 5) cells markers. We observed higher coexpression of GFP signal with CD31 or vWF immunoreactivity, when compared to the cells coexpressing both GFP signal and α-SMA labeling. The ratio was 4:1 between CD31 or vWF and α-SMA. Our results indicate that most of the GFP-BM-MSCs appear to express mainly CD31 or vWF (data not shown) in the infarcted area (Figure 5).

Bottom Line: This study was aimed to assess the effects of bone marrow mesenchymal stem cells (BM-MSCs) infused after MCAO on rat pial microcirculation.In conclusion, transient MCAO induced pial vascular remodeling characterized by arteriolar anastomotic arcades (originated from preexistent arterioles in penumbra area) able to overlap the ischemic core supplying blood to the neuronal tissue.BM-MSCs appear to accelerate angiogenic processes facilitating new vessel formation; this mechanism was promoted by an increase in VEGF and eNOS expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Medicine and Surgery, "Federico II" University Medical School Naples, Italy.

ABSTRACT
Previous studies have shown that the pial microcirculation remodeling improves neurological outcome after middle cerebral artery occlusion (MCAO), accompanied by higher expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), modulating in vivo angiogenesis. This study was aimed to assess the effects of bone marrow mesenchymal stem cells (BM-MSCs) infused after MCAO on rat pial microcirculation. Animals were subjected to 2 h MCAO followed by BM-MSCs infusion into internal carotid artery. Pial microcirculation was observed at different reperfusion times by fluorescence microscopy. Geometric characteristics of arteriolar networks, permeability increase, leukocyte adhesion, perfused capillary density, VEGF, and endothelial nitric oxide synthase (e-NOS) expression were evaluated. Green fluorescent protein (GFP)-BM-MSCs were used to evaluate their distribution and cell phenotype development during reperfusion. BM-MSCs stimulated a geometric rearrangement of pial networks with formation of new anastomotic vessels sprouting from preexistent arterioles in the penumbra at 7-14-28 days of reperfusion. At the same time VEGF and eNOS expression increased. GFP-BM-MSCs appear to be involved in endothelial and smooth muscle cell programming in the infarcted area. In conclusion, transient MCAO induced pial vascular remodeling characterized by arteriolar anastomotic arcades (originated from preexistent arterioles in penumbra area) able to overlap the ischemic core supplying blood to the neuronal tissue. BM-MSCs appear to accelerate angiogenic processes facilitating new vessel formation; this mechanism was promoted by an increase in VEGF and eNOS expression.

No MeSH data available.


Related in: MedlinePlus