Monocytes are essential for the neuroprotective effect of human cord blood cells following middle cerebral artery occlusion in rat.
Systemic administration of human umbilical cord blood (HUCB) mononuclear cells (MNC) following middle cerebral artery occlusion (MCAO) in the rat reduces infarct size and, more importantly, restores motor function. The HUCB cell preparation is composed of immature T-cells, B-cells, monocytes and stem cells. In this study we examined whether the beneficial effects of HUCB injection were attributable to one of these cell types. Male Sprague Dawley rats underwent permanent MCAO followed 48 h later by intravenous administration of HUCB MNC preparations depleted of either CD14(+) monocytes, CD133(+) stem cells, CD2(+) T-cells or CD19(+) B cells. Motor function was measured prior to MCAO and 30 days post-stroke. When CD14(+) monocytes were depleted from the HUCB MNC, activity and motor asymmetry were similar to the MCAO only treated animals. Monocyte depletion prevented HUCB cell treatment from reducing infarct size while monocyte enrichment was sufficient to reduce infarct size. Administration of monocyte-depleted HUCB cells did not suppress Iba1 labeling of microglia in the infarcted area relative to treatment with the whole HUCB preparation. These data demonstrate that the HUCB monocytes provide the majority of the efficacy in reducing infarct volume and promoting functional recovery.
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States; Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States.
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Womble
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States; Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States.
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Green
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States; Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States.
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Shahaduzzaman
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States.
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Grieco
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States; Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States.
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Sanberg
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States; Department of Molecular Pharmacology and Physiology, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States.
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Pennypacker
Center for Excellence in Aging and Brain Repair,University of South Florida, Tampa, FL 33612, United States; Department of Neurosurgery and Brain Repair, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States; Department of Molecular Pharmacology and Physiology, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, United States. Electronic address: awilling@health.usf.edu.
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Willing
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000637:transplantation; D018801:CD2 Antigens / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000637:transplantation*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000637:transplantation*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation
D000071916:AC133 Antigen; D015703:Antigens, CD; D018941:Antigens, CD19; D018801:CD2 Antigens; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat
Behavior; Cerebral ischemia; Cord blood; Infarct; Microglia; Monocytes