title: Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke.
abstract: OBJECTIVE
  Adult stem cell therapy is an experimental stroke treatment. Here, we assessed homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) in chronic stroke.
  
  
  METHODS
  At 60 days post stroke, adult Sprague-Dawley rats received intravenous hBMSCs (4×10(6) labeled or nonlabeled cells) or vehicle (saline). A sham surgery group served as additional control. In vivo imaging was conducted between 1 hour and 11 days post transplantation, followed by histological examination.
  
  
  RESULTS
  Labeled hBMSCs migrated to spleen which emitted significantly higher fluorescent signal across all time points, especially during the first hour, and were modestly detected in the head region at the 12 hours and 11 days, compared with nonlabeled hBMSCs and vehicle-infused stroke animals, or sham (P<0.05). At 11 days post transplantation, ex vivo imaging confirmed preferential hBMSC migration to the spleen over the brain. 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. Unbiased stereology showed significant 75% and 60% decrements in major histocompatibility complex II-activated inflammatory cells in gray and white matter, and a 43% diminution in tumor necrosis factor-α cell density in the spleen of transplanted stroke animals compared with vehicle-infused stroke animals (P<0.05). 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.
  
  
  CONCLUSIONS
  hBMSC transplantation is therapeutic in chronic stroke possibly by abrogating the inflammation-plagued secondary cell death.
authors.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.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Acosta
authors.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.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.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.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Hoover
authors.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.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.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. cborlong@health.usf.edu.
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D007249:Inflammation / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen; D020521:Stroke / Q000628:therapy*
keywords: brain ischemia; imaging; inflammation; regeneration; stem cells