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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

Preferential in vivo migration of hBMSC-DiR+ to spleen in chronic stroke. Representative images of in vivo fluorescence imaging of intravenously transplanted hBMSCs in an experimental model of chronic stroke at 1, 4, 12, 24, 48, and 72 hours and 11 days post transplantation. Photographs were taken from ventral (body) and dorsal positions (head). Imaging analyses revealed that hBMSC-DiR+ cells displayed a preferential migration to the spleen over the brain when transplanted at 60 days post stroke (***P<0.001). A and B, Within the hBMSC-DiR+ transplanted stroke group, there were no significant differences in fluorescent signals across all time points except the first hour, whereby a higher emitted signal was found within spleen and on day 11 where the signal was greatly reduced relative to other time points (*P<0.05). C and D, Fluorescent signals were also elevated in the head area at 12 hours and 11 days post transplantation (**P<0.01 and ***P<0.001). There were no fluorescent signals detected in the spleen and head region of hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals. Radiant efficiency={(p/s/cm2/sr)/(μW/cm2)}, color scale: min=1.54×108; max=3.2×108. *P<0.05, **P<0.01, and ***P<0.001. Data are expressed as mean±SEM. DiR indicates 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricbocyanine iodide; and hBMSC, homing and anti-inflammatory effects of bone marrow stromal cells.
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Figure 1: Preferential in vivo migration of hBMSC-DiR+ to spleen in chronic stroke. Representative images of in vivo fluorescence imaging of intravenously transplanted hBMSCs in an experimental model of chronic stroke at 1, 4, 12, 24, 48, and 72 hours and 11 days post transplantation. Photographs were taken from ventral (body) and dorsal positions (head). Imaging analyses revealed that hBMSC-DiR+ cells displayed a preferential migration to the spleen over the brain when transplanted at 60 days post stroke (***P<0.001). A and B, Within the hBMSC-DiR+ transplanted stroke group, there were no significant differences in fluorescent signals across all time points except the first hour, whereby a higher emitted signal was found within spleen and on day 11 where the signal was greatly reduced relative to other time points (*P<0.05). C and D, Fluorescent signals were also elevated in the head area at 12 hours and 11 days post transplantation (**P<0.01 and ***P<0.001). There were no fluorescent signals detected in the spleen and head region of hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals. Radiant efficiency={(p/s/cm2/sr)/(μW/cm2)}, color scale: min=1.54×108; max=3.2×108. *P<0.05, **P<0.01, and ***P<0.001. Data are expressed as mean±SEM. DiR indicates 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricbocyanine iodide; and hBMSC, homing and anti-inflammatory effects of bone marrow stromal cells.

Mentions: ANOVA revealed that there was a significant treatment effects based on fluorescent signals detected in the spleen (F3,11=4.953, P<0.001; Figure 1A and 1B). Pairwise comparison using post hoc tests revealed that hBMSC-DiR+ transplanted cells migrated to the spleen, emitting significantly higher fluorescent signals across all time points compared with hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals (P<0.05). Moreover, within the hBMSC-DiR+ transplanted stroke group, there were no significant differences in fluorescent signals across all time points except the first hour, whereby a higher emitted signal was found within spleen and on day 11 where the signal was greatly reduced relative to other time points (P<0.05). The signal that we detected from the transplanted group was specific for the DiR labeling because hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals, which were similarly subjected to the imaging assay displayed no detectable fluorescent signal (Figure 1A and 1B).


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)

Preferential in vivo migration of hBMSC-DiR+ to spleen in chronic stroke. Representative images of in vivo fluorescence imaging of intravenously transplanted hBMSCs in an experimental model of chronic stroke at 1, 4, 12, 24, 48, and 72 hours and 11 days post transplantation. Photographs were taken from ventral (body) and dorsal positions (head). Imaging analyses revealed that hBMSC-DiR+ cells displayed a preferential migration to the spleen over the brain when transplanted at 60 days post stroke (***P<0.001). A and B, Within the hBMSC-DiR+ transplanted stroke group, there were no significant differences in fluorescent signals across all time points except the first hour, whereby a higher emitted signal was found within spleen and on day 11 where the signal was greatly reduced relative to other time points (*P<0.05). C and D, Fluorescent signals were also elevated in the head area at 12 hours and 11 days post transplantation (**P<0.01 and ***P<0.001). There were no fluorescent signals detected in the spleen and head region of hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals. Radiant efficiency={(p/s/cm2/sr)/(μW/cm2)}, color scale: min=1.54×108; max=3.2×108. *P<0.05, **P<0.01, and ***P<0.001. Data are expressed as mean±SEM. DiR indicates 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricbocyanine iodide; and hBMSC, homing and anti-inflammatory effects of bone marrow stromal cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Preferential in vivo migration of hBMSC-DiR+ to spleen in chronic stroke. Representative images of in vivo fluorescence imaging of intravenously transplanted hBMSCs in an experimental model of chronic stroke at 1, 4, 12, 24, 48, and 72 hours and 11 days post transplantation. Photographs were taken from ventral (body) and dorsal positions (head). Imaging analyses revealed that hBMSC-DiR+ cells displayed a preferential migration to the spleen over the brain when transplanted at 60 days post stroke (***P<0.001). A and B, Within the hBMSC-DiR+ transplanted stroke group, there were no significant differences in fluorescent signals across all time points except the first hour, whereby a higher emitted signal was found within spleen and on day 11 where the signal was greatly reduced relative to other time points (*P<0.05). C and D, Fluorescent signals were also elevated in the head area at 12 hours and 11 days post transplantation (**P<0.01 and ***P<0.001). There were no fluorescent signals detected in the spleen and head region of hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals. Radiant efficiency={(p/s/cm2/sr)/(μW/cm2)}, color scale: min=1.54×108; max=3.2×108. *P<0.05, **P<0.01, and ***P<0.001. Data are expressed as mean±SEM. DiR indicates 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricbocyanine iodide; and hBMSC, homing and anti-inflammatory effects of bone marrow stromal cells.
Mentions: ANOVA revealed that there was a significant treatment effects based on fluorescent signals detected in the spleen (F3,11=4.953, P<0.001; Figure 1A and 1B). Pairwise comparison using post hoc tests revealed that hBMSC-DiR+ transplanted cells migrated to the spleen, emitting significantly higher fluorescent signals across all time points compared with hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals (P<0.05). Moreover, within the hBMSC-DiR+ transplanted stroke group, there were no significant differences in fluorescent signals across all time points except the first hour, whereby a higher emitted signal was found within spleen and on day 11 where the signal was greatly reduced relative to other time points (P<0.05). The signal that we detected from the transplanted group was specific for the DiR labeling because hBMSC-DiR− transplanted and vehicle-infused stroke animals, and sham animals, which were similarly subjected to the imaging assay displayed no detectable fluorescent signal (Figure 1A and 1B).

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