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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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Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) reduced tumor necrosis factor-α (TNF-α) density in the spleen of stroke animals. A, Quantitative analysis of TNF-α expression in the spleen revealed a significant upregulation of TNF-α density in vehicle-infused stroke animals. In contrast, hBMSC treatment promoted a 40% downregulation of TNF-α density in the spleen (*P<0.05). B, Confocal photomicrographs of positive expression of TNF-α (green) and Hoechst (blue) in the spleen of vehicle-infused (top) and transplanted stroke animals (bottom), indicating decreased expression of TNF-α in the spleen of hBMSC-transplanted stroke animals relative to vehicle-infused stroke animals. C, Correlations found between reduction in striatal infarct and peri-infarct areas, downregulation of MHCII+ cells in brain, and decreased density of TNF-α in the spleen, and the number of hBMSCs that migrated to the spleen (% infarct area: Pearson r=−0.8678, R2=−0.7531, P<0.01; % peri-infarct area: Pearson r=−0.8282, R2=−0.6859, P<0.05; the volume of MHCII+ activated cells in the striatum: Pearson r=−0.8656, R2=−0.7492, P<0.05; the density of TNF-α expression in the spleen: Pearson r=−0.8381, R2=−0.7025, P<0.05). Scale bar=50 μm. *P<0.05. Data are expressed as mean±SEM.
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Figure 6: Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) reduced tumor necrosis factor-α (TNF-α) density in the spleen of stroke animals. A, Quantitative analysis of TNF-α expression in the spleen revealed a significant upregulation of TNF-α density in vehicle-infused stroke animals. In contrast, hBMSC treatment promoted a 40% downregulation of TNF-α density in the spleen (*P<0.05). B, Confocal photomicrographs of positive expression of TNF-α (green) and Hoechst (blue) in the spleen of vehicle-infused (top) and transplanted stroke animals (bottom), indicating decreased expression of TNF-α in the spleen of hBMSC-transplanted stroke animals relative to vehicle-infused stroke animals. C, Correlations found between reduction in striatal infarct and peri-infarct areas, downregulation of MHCII+ cells in brain, and decreased density of TNF-α in the spleen, and the number of hBMSCs that migrated to the spleen (% infarct area: Pearson r=−0.8678, R2=−0.7531, P<0.01; % peri-infarct area: Pearson r=−0.8282, R2=−0.6859, P<0.05; the volume of MHCII+ activated cells in the striatum: Pearson r=−0.8656, R2=−0.7492, P<0.05; the density of TNF-α expression in the spleen: Pearson r=−0.8381, R2=−0.7025, P<0.05). Scale bar=50 μm. *P<0.05. Data are expressed as mean±SEM.

Mentions: TNF-α expression in the spleen was analyzed using immunofluorescence to reveal anti-inflammatory effects of hBMSCs on splenic function. The mean TNF-α density in the spleen was highly elevated in vehicle-infused stroke animals which was significantly downregulated by hBMSC transplantation (Student t test, P<0.05; Figure 6A and 6B).


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 (hBMSCs) reduced tumor necrosis factor-α (TNF-α) density in the spleen of stroke animals. A, Quantitative analysis of TNF-α expression in the spleen revealed a significant upregulation of TNF-α density in vehicle-infused stroke animals. In contrast, hBMSC treatment promoted a 40% downregulation of TNF-α density in the spleen (*P<0.05). B, Confocal photomicrographs of positive expression of TNF-α (green) and Hoechst (blue) in the spleen of vehicle-infused (top) and transplanted stroke animals (bottom), indicating decreased expression of TNF-α in the spleen of hBMSC-transplanted stroke animals relative to vehicle-infused stroke animals. C, Correlations found between reduction in striatal infarct and peri-infarct areas, downregulation of MHCII+ cells in brain, and decreased density of TNF-α in the spleen, and the number of hBMSCs that migrated to the spleen (% infarct area: Pearson r=−0.8678, R2=−0.7531, P<0.01; % peri-infarct area: Pearson r=−0.8282, R2=−0.6859, P<0.05; the volume of MHCII+ activated cells in the striatum: Pearson r=−0.8656, R2=−0.7492, P<0.05; the density of TNF-α expression in the spleen: Pearson r=−0.8381, R2=−0.7025, P<0.05). Scale bar=50 μm. *P<0.05. Data are expressed as mean±SEM.
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Related In: Results  -  Collection

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Figure 6: Homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) reduced tumor necrosis factor-α (TNF-α) density in the spleen of stroke animals. A, Quantitative analysis of TNF-α expression in the spleen revealed a significant upregulation of TNF-α density in vehicle-infused stroke animals. In contrast, hBMSC treatment promoted a 40% downregulation of TNF-α density in the spleen (*P<0.05). B, Confocal photomicrographs of positive expression of TNF-α (green) and Hoechst (blue) in the spleen of vehicle-infused (top) and transplanted stroke animals (bottom), indicating decreased expression of TNF-α in the spleen of hBMSC-transplanted stroke animals relative to vehicle-infused stroke animals. C, Correlations found between reduction in striatal infarct and peri-infarct areas, downregulation of MHCII+ cells in brain, and decreased density of TNF-α in the spleen, and the number of hBMSCs that migrated to the spleen (% infarct area: Pearson r=−0.8678, R2=−0.7531, P<0.01; % peri-infarct area: Pearson r=−0.8282, R2=−0.6859, P<0.05; the volume of MHCII+ activated cells in the striatum: Pearson r=−0.8656, R2=−0.7492, P<0.05; the density of TNF-α expression in the spleen: Pearson r=−0.8381, R2=−0.7025, P<0.05). Scale bar=50 μm. *P<0.05. Data are expressed as mean±SEM.
Mentions: TNF-α expression in the spleen was analyzed using immunofluorescence to reveal anti-inflammatory effects of hBMSCs on splenic function. The mean TNF-α density in the spleen was highly elevated in vehicle-infused stroke animals which was significantly downregulated by hBMSC transplantation (Student t test, P<0.05; Figure 6A and 6B).

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