BACKGROUND AND PURPOSE: Systemic injection of hematopoietic stem cells after ischemic cardiac or neural lesions is one approach to promote tissue repair. However, mechanisms of possible protective or reparative effects are poorly understood. In this study we analyzed the effect of lineage-negative bone marrow-derived hematopoietic stem and precursor cells (Lin(-)-HSCs) on ischemic brain injury in mice. METHODS: Lin(-)-HSCs were injected intravenously at 24 hours after onset of a 45-minute transient cerebral ischemia. Effects of Lin(-)-HSCs injection on infarct size, apoptotic cell death, postischemic inflammation and cytokine gene transcription were analyzed. RESULTS: Green fluorescent protein (GFP)-marked Lin(-)-HSCs were detected at 24 hours after injection in the spleen and later in ischemic brain parenchyma, expressing microglial but no neural marker proteins. Tissue injury assessment showed significantly smaller infarct volumes and less apoptotic neuronal cell death in peri-infarct areas of Lin(-)-HSC-treated animals. Analysis of immune cell infiltration in ischemic hemispheres revealed a reduction of invading T cells and macrophages in treated mice. Moreover, Lin(-)-HSC therapy counter-regulated proinflammatory cytokine and chemokine receptor gene transcription within the spleen. CONCLUSIONS: Our data demonstrate that systemically applied Lin(-)-HSCs reduce cerebral postischemic inflammation, attenuate peripheral immune activation and mediate neuroprotection after ischemic stroke.
BACKGROUND AND PURPOSE: Systemic injection of hematopoietic stem cells after ischemic cardiac or neural lesions is one approach to promote tissue repair. However, mechanisms of possible protective or reparative effects are poorly understood. In this study we analyzed the effect of lineage-negative bone marrow-derived hematopoietic stem and precursor cells (Lin(-)-HSCs) on ischemic brain injury in mice. METHODS: Lin(-)-HSCs were injected intravenously at 24 hours after onset of a 45-minute transient cerebral ischemia. Effects of Lin(-)-HSCs injection on infarct size, apoptotic cell death, postischemic inflammation and cytokine gene transcription were analyzed. RESULTS: Green fluorescent protein (GFP)-marked Lin(-)-HSCs were detected at 24 hours after injection in the spleen and later in ischemic brain parenchyma, expressing microglial but no neural marker proteins. Tissue injury assessment showed significantly smaller infarct volumes and less apoptotic neuronal cell death in peri-infarct areas of Lin(-)-HSC-treated animals. Analysis of immune cell infiltration in ischemic hemispheres revealed a reduction of invading T cells and macrophages in treated mice. Moreover, Lin(-)-HSC therapy counter-regulated proinflammatory cytokine and chemokine receptor gene transcription within the spleen. CONCLUSIONS: Our data demonstrate that systemically applied Lin(-)-HSCs reduce cerebral postischemic inflammation, attenuate peripheral immune activation and mediate neuroprotection after ischemic stroke.
Authors: Farhaan S Vahidy; Kaushik N Parsha; Mohammad H Rahbar; MinJae Lee; Thanh-Tung Bui; Claude Nguyen; Andrew D Barreto; Arvind B Bambhroliya; Preeti Sahota; Bing Yang; Jaroslaw Aronowski; Sean I Savitz Journal: J Cereb Blood Flow Metab Date: 2015-10-02 Impact factor: 6.200
Authors: Erja Kerkelä; Tanja Hakkarainen; Tuomas Mäkelä; Mari Raki; Oleg Kambur; Lotta Kilpinen; Janne Nikkilä; Siri Lehtonen; Ilja Ritamo; Roni Pernu; Mika Pietilä; Reijo Takalo; Tatu Juvonen; Kim Bergström; Eija Kalso; Leena Valmu; Saara Laitinen; Petri Lehenkari; Johanna Nystedt Journal: Stem Cells Transl Med Date: 2013-06-03 Impact factor: 6.940
Authors: Peter A Walker; Phillip A Letourneau; Supinder Bedi; Shinil K Shah; Fernando Jimenez; Charles S Cox Journal: World J Stem Cells Date: 2011-02-26 Impact factor: 5.326