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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: 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.

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

Computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 1 day of reperfusion (I-MSCs-1R). GFP- BM-MSCs were detected into the vessels, as indicated by the white arrow (A). In (B), computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 7 days of reperfusion (I-MSCs-7R). Interstitial fluorescent GFP-BM- MSCs were organized to form straight lines as a track for new vessel formation (white dashed line).
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Figure 4: Computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 1 day of reperfusion (I-MSCs-1R). GFP- BM-MSCs were detected into the vessels, as indicated by the white arrow (A). In (B), computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 7 days of reperfusion (I-MSCs-7R). Interstitial fluorescent GFP-BM- MSCs were organized to form straight lines as a track for new vessel formation (white dashed line).

Mentions: GFP-positive cells infused after MCA occlusion were observed in all ischemic and penumbra areas, in close association with blood vessels in pilot experiments. After 1 h of reperfusion GFP-BM-MSCs were largely found in arterioles of the penumbra area as observed in three rats utilized to assess the primary cell localization, not reported in the experimental groups. Disruption of the BBB after MCAO, as shown by microvascular permeability increase, was accompanied by selective entry of BM-MSCs into ischemic brain compared with non-ischemic contralateral hemisphere. At 7 days, GFP-BM-MSCs were mainly found in the damaged hemisphere. Moreover, these cells were organized in penumbra area to form straight-like lines, suggesting a track for tube-like vessel formation (Figure 4). In the last group of treated animals, after 28 days of reperfusion marked fluorescence along the vessel walls was observed with a reduced number of cells into the penumbra area and interstitium.


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)

Computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 1 day of reperfusion (I-MSCs-1R). GFP- BM-MSCs were detected into the vessels, as indicated by the white arrow (A). In (B), computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 7 days of reperfusion (I-MSCs-7R). Interstitial fluorescent GFP-BM- MSCs were organized to form straight lines as a track for new vessel formation (white dashed line).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 1 day of reperfusion (I-MSCs-1R). GFP- BM-MSCs were detected into the vessels, as indicated by the white arrow (A). In (B), computer-assisted image of pial microvascular network in a rat subjected to 2 h MCAO and infused with GFP-BM-MSCs and observed after 7 days of reperfusion (I-MSCs-7R). Interstitial fluorescent GFP-BM- MSCs were organized to form straight lines as a track for new vessel formation (white dashed line).
Mentions: GFP-positive cells infused after MCA occlusion were observed in all ischemic and penumbra areas, in close association with blood vessels in pilot experiments. After 1 h of reperfusion GFP-BM-MSCs were largely found in arterioles of the penumbra area as observed in three rats utilized to assess the primary cell localization, not reported in the experimental groups. Disruption of the BBB after MCAO, as shown by microvascular permeability increase, was accompanied by selective entry of BM-MSCs into ischemic brain compared with non-ischemic contralateral hemisphere. At 7 days, GFP-BM-MSCs were mainly found in the damaged hemisphere. Moreover, these cells were organized in penumbra area to form straight-like lines, suggesting a track for tube-like vessel formation (Figure 4). In the last group of treated animals, after 28 days of reperfusion marked fluorescence along the vessel walls was observed with a reduced number of cells into the penumbra area and interstitium.

Bottom Line: 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.

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