Hematopoietic stem cells reduce postischemic inflammation and ameliorate ischemic brain injury.
OBJECTIVE
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.
Schwarting
Sönke
S
Department of Neurology, Cerebral Ischemia Research Group, University of Göttingen Medical School, Göttingen, Germany.
Litwak
Sara
S
Hao
Wenlin
W
Bähr
Mathias
M
Weise
Jens
J
Neumann
Harald
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D002465:Cell Movement / Q000276:immunology; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism