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Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke.

Acosta SA, Tajiri N, Hoover J, Kaneko Y, Borlongan CV - Stroke (2015)

Bottom Line: Hematoxylin and eosin staining revealed significant 15% and 30% reductions in striatal infarct and peri-infarct area, and a trend of rescue against neuronal loss in the hippocampus.Human antigen immunostaining revealed 0.03% hBMSCs survived in spleen and only 0.0007% in brain.MSC migration to spleen, but not brain, inversely correlated with reduced infarct, peri-infarct, and inflammation. hBMSC transplantation is therapeutic in chronic stroke possibly by abrogating the inflammation-plagued secondary cell death.

View Article: PubMed Central - PubMed

Affiliation: From the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa.

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Related in: MedlinePlus

Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSC) transplantation ameliorates neuroinflammation in gray and white matter areas in chronic stroke. A, Stereological analysis of MHCII+ cells estimated volume in striatum, subventricular zone (SVZ), and hilus revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all gray matter areas analyzed (***P<0.0001), except SVZ (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral gray matter areas of vehicle-infused stroke animals (P<0.0001) and hBMSC-transplanted stroke animals compared with sham animals (P<0.05). hBMSC transplantation caused a 35%, 28%, and 90% reduction of the estimated volume of MHC+ cells in the ipsilateral striatum, SVZ, and hilus, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (**P<0.01; **P<0.01; ***P<0.001). B, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells in striatum, SVZ, and hilus. C, Effects of hBMSC transplantation on MHCII+ cells in white matter regions. Stereological analysis of MHCII+ cells estimated volume in corpus callosum, internal capsule, and fornix revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all white matter areas analyzed (***P<0.0001), except corpus callosum (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral side of vehicle-infused stroke animals (***P<0.0001) and hBMSC-transplanted stroke animals across all white matter areas analyzed compared with sham animals (*P<0.05). hBMSC transplantation caused a 60%, 38%, and 70% reduction of the estimated volume of MHCII+ cells in the ipsilateral corpus callosum, internal capsule, and fornix, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (***P<0.001). D, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells. Scale bar=50 μm. *P<0.05, **P<0.01, and ***P<0.001; ns=not significant. Data are expressed as mean±SEM. MHCII indicates major histocompatibility complex II.
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Figure 4: Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSC) transplantation ameliorates neuroinflammation in gray and white matter areas in chronic stroke. A, Stereological analysis of MHCII+ cells estimated volume in striatum, subventricular zone (SVZ), and hilus revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all gray matter areas analyzed (***P<0.0001), except SVZ (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral gray matter areas of vehicle-infused stroke animals (P<0.0001) and hBMSC-transplanted stroke animals compared with sham animals (P<0.05). hBMSC transplantation caused a 35%, 28%, and 90% reduction of the estimated volume of MHC+ cells in the ipsilateral striatum, SVZ, and hilus, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (**P<0.01; **P<0.01; ***P<0.001). B, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells in striatum, SVZ, and hilus. C, Effects of hBMSC transplantation on MHCII+ cells in white matter regions. Stereological analysis of MHCII+ cells estimated volume in corpus callosum, internal capsule, and fornix revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all white matter areas analyzed (***P<0.0001), except corpus callosum (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral side of vehicle-infused stroke animals (***P<0.0001) and hBMSC-transplanted stroke animals across all white matter areas analyzed compared with sham animals (*P<0.05). hBMSC transplantation caused a 60%, 38%, and 70% reduction of the estimated volume of MHCII+ cells in the ipsilateral corpus callosum, internal capsule, and fornix, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (***P<0.001). D, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells. Scale bar=50 μm. *P<0.05, **P<0.01, and ***P<0.001; ns=not significant. Data are expressed as mean±SEM. MHCII indicates major histocompatibility complex II.

Mentions: The estimated volume of MHCII+ activated cells was quantified using stereological techniques. Several brain regions were examined to reveal stroke-induced neuroinflammation in both gray and white matter areas (Figure 4A and 4B). ANOVA revealed overall significant treatment effect on inflammation in the subcortical regions as evidenced by MHCII immunostaining in all gray matter regions examined here as follows: striatum (F5,24=10.13, P<0.0001); subventricular zone (F5,24=140.7, P<0.0001); and hilus (F5, 24=16.51, P<0.0001). Post hoc test revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all gray matter areas analyzed (P<0.0001), except subventricular zone (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral gray matter areas of vehicle-infused stroke animals compared with sham animals (P<0.0001). There were also significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral side of hBMSC-transplanted stroke animals across all gray matter areas analyzed compared with sham animals (P<0.05; Figure 4A and 4B). There were significant reductions in activated MHCII+ cells in both ipsilateral and contralateral side of hBMSC-transplanted stroke animals across all gray matter areas analyzed compared with the ipsilateral and contralateral side of vehicle-infused stroke animals (P<0.001), indicating efficacy of the treatment. Moreover, the reduction of activated MHCII+ cells in the ipsilateral side of hBMSC-transplanted stroke animals did not significantly differ to their contralateral side across all gray matter areas analyzed (P>0.05).


Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke.

Acosta SA, Tajiri N, Hoover J, Kaneko Y, Borlongan CV - Stroke (2015)

Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSC) transplantation ameliorates neuroinflammation in gray and white matter areas in chronic stroke. A, Stereological analysis of MHCII+ cells estimated volume in striatum, subventricular zone (SVZ), and hilus revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all gray matter areas analyzed (***P<0.0001), except SVZ (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral gray matter areas of vehicle-infused stroke animals (P<0.0001) and hBMSC-transplanted stroke animals compared with sham animals (P<0.05). hBMSC transplantation caused a 35%, 28%, and 90% reduction of the estimated volume of MHC+ cells in the ipsilateral striatum, SVZ, and hilus, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (**P<0.01; **P<0.01; ***P<0.001). B, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells in striatum, SVZ, and hilus. C, Effects of hBMSC transplantation on MHCII+ cells in white matter regions. Stereological analysis of MHCII+ cells estimated volume in corpus callosum, internal capsule, and fornix revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all white matter areas analyzed (***P<0.0001), except corpus callosum (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral side of vehicle-infused stroke animals (***P<0.0001) and hBMSC-transplanted stroke animals across all white matter areas analyzed compared with sham animals (*P<0.05). hBMSC transplantation caused a 60%, 38%, and 70% reduction of the estimated volume of MHCII+ cells in the ipsilateral corpus callosum, internal capsule, and fornix, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (***P<0.001). D, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells. Scale bar=50 μm. *P<0.05, **P<0.01, and ***P<0.001; ns=not significant. Data are expressed as mean±SEM. MHCII indicates major histocompatibility complex II.
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Figure 4: Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSC) transplantation ameliorates neuroinflammation in gray and white matter areas in chronic stroke. A, Stereological analysis of MHCII+ cells estimated volume in striatum, subventricular zone (SVZ), and hilus revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all gray matter areas analyzed (***P<0.0001), except SVZ (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral gray matter areas of vehicle-infused stroke animals (P<0.0001) and hBMSC-transplanted stroke animals compared with sham animals (P<0.05). hBMSC transplantation caused a 35%, 28%, and 90% reduction of the estimated volume of MHC+ cells in the ipsilateral striatum, SVZ, and hilus, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (**P<0.01; **P<0.01; ***P<0.001). B, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells in striatum, SVZ, and hilus. C, Effects of hBMSC transplantation on MHCII+ cells in white matter regions. Stereological analysis of MHCII+ cells estimated volume in corpus callosum, internal capsule, and fornix revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all white matter areas analyzed (***P<0.0001), except corpus callosum (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral side of vehicle-infused stroke animals (***P<0.0001) and hBMSC-transplanted stroke animals across all white matter areas analyzed compared with sham animals (*P<0.05). hBMSC transplantation caused a 60%, 38%, and 70% reduction of the estimated volume of MHCII+ cells in the ipsilateral corpus callosum, internal capsule, and fornix, respectively, relative to the ipsilateral side of the same regions of vehicle-infused stroke animals (***P<0.001). D, Photomicrographs are representative coronal brain sections ipsilateral to injury stained with MHCII 11 days post hBMSC transplantation. Arrows indicate positive staining for activated MHCII+ cells. Scale bar=50 μm. *P<0.05, **P<0.01, and ***P<0.001; ns=not significant. Data are expressed as mean±SEM. MHCII indicates major histocompatibility complex II.
Mentions: The estimated volume of MHCII+ activated cells was quantified using stereological techniques. Several brain regions were examined to reveal stroke-induced neuroinflammation in both gray and white matter areas (Figure 4A and 4B). ANOVA revealed overall significant treatment effect on inflammation in the subcortical regions as evidenced by MHCII immunostaining in all gray matter regions examined here as follows: striatum (F5,24=10.13, P<0.0001); subventricular zone (F5,24=140.7, P<0.0001); and hilus (F5, 24=16.51, P<0.0001). Post hoc test revealed significant upregulation of activated MHCII+ cells in the ipsilateral side of vehicle-infused stroke animals compared with their contralateral side across all gray matter areas analyzed (P<0.0001), except subventricular zone (P>0.05). There were significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral gray matter areas of vehicle-infused stroke animals compared with sham animals (P<0.0001). There were also significant upregulation of activated MHCII+ cells in both ipsilateral and contralateral side of hBMSC-transplanted stroke animals across all gray matter areas analyzed compared with sham animals (P<0.05; Figure 4A and 4B). There were significant reductions in activated MHCII+ cells in both ipsilateral and contralateral side of hBMSC-transplanted stroke animals across all gray matter areas analyzed compared with the ipsilateral and contralateral side of vehicle-infused stroke animals (P<0.001), indicating efficacy of the treatment. Moreover, the reduction of activated MHCII+ cells in the ipsilateral side of hBMSC-transplanted stroke animals did not significantly differ to their contralateral side across all gray matter areas analyzed (P>0.05).

Bottom Line: Hematoxylin and eosin staining revealed significant 15% and 30% reductions in striatal infarct and peri-infarct area, and a trend of rescue against neuronal loss in the hippocampus.Human antigen immunostaining revealed 0.03% hBMSCs survived in spleen and only 0.0007% in brain.MSC migration to spleen, but not brain, inversely correlated with reduced infarct, peri-infarct, and inflammation. hBMSC transplantation is therapeutic in chronic stroke possibly by abrogating the inflammation-plagued secondary cell death.

View Article: PubMed Central - PubMed

Affiliation: From the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa.

Show MeSH
Related in: MedlinePlus