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(Stroke. 2008;39:2867.)
© 2008 American Heart Association, Inc.

Original Contributions

Hematopoietic Stem Cells Reduce Postischemic Inflammation and Ameliorate Ischemic Brain Injury

Sönke Schwarting, MD; Sara Litwak, PhD; Wenlin Hao, MD; Mathias Bähr, MD; Jens Weise, MD Harald Neumann, MD

From Cerebral Ischemia Research Group (S.S., M.B., J.W.), Department of Neurology, University of Göttingen Medical School, Göttingen, Germany; European Neuroscience Institute Göttingen (W.H., H.N.), Göttingen, Germany; Institute of Reconstructive Neurobiology (S.L., H.N.), University Bonn LIFE & BRAIN Center, University Bonn and Hertie-Foundation, Bonn, Germany; Department of Neurology (J.W.), University of Jena Medical School, Jena, Germany.

Correspondence to Harald Neumann, E-mail hneuman1{at}uni-bonn.de; or Jens Weise, E-mail JENS.WEISE@med.uni-jena.de

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.

Key Words: cell therapy • cerebral ischemia • hematopoietic stem cells • neuroprotection • postischemic inflammation