Changes in Host Blood Factors and Brain Glia Accompanying the Functional Recovery after Systemic Administration of Bone Marrow Stem Cells in Ischemic Stroke Rats

Cell Transplantation

Article

Robert Rosenwasser¹  Ming Yang²  Lorraine Iacovitti³  Lynn A. Heine⁴  Xiaotao Wei⁵  Jing Li⁵ 

[1] Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA;Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA;Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA; Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA, USA;Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA;Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA, USA;

关键词: Bone marrow transplantation;    Middle cerebral artery occlusion;    Stroke;    Inflammatory factors;    Microglia;    Reactive astrocytes;   

DOI  :  10.3727/096368910X503415

 received in 2009-10-01, accepted in 2010-04-15,  发布年份 2010

来源: Sage Journals

【 摘 要 】

In this study, we examined the effects of systemic administration of rat or human bone marrow stromal stem cells (MSC) at early and later times following middle cerebral artery occlusion (MCAO) on blood cytokines/growth factors, brain glia, and motor behavior in rats. Rats were tail vein injected with rat (r) and human (h) MSCs at 1 or 7 days post-MCAO. In some rats (N = 4) MSCs isolated from transgenic GFP rats were used to track the migration of cells peripherally and centrally at 2.5 and 28 days. Motor behavior was assessed using the modified Neurological Severity Score/climbing test at various time points before and after MCAO and transplantation. Prior to sacrifice at 1, 7, or 28 days post-MCAO, blood serum was collected for cytokine array analysis. Brains were analyzed for markers of activated microglia (CD11) and reactive astrocytes (GFAP). Administration of either allogeneic (rMSCs) or xenogeneic (hMSCs) stem cells produced a significant recovery of motor behavior after MCAO, with cells delivered at 1 day having greater effect than those at 7 days. Correlated with recovery was an amplification in activated microglia, reactive astrocytes, and new blood vessels in the infarct region, resulting in greater preservation in brain integrity. Concomitantly, expression of blood cytokines/chemokines (IL-13, MMP2, MIP) and growth factors/receptors (VEGF, neuropilin, EPOR, TROY, NGFR, RAGE) were modified following MSC administration. Because only rare GFP-labeled MSCs were observed in the brain, these effects did not depend on the central incorporation of stem cells. The early systemic administration of allogeneic or xenogeneic MSCs soon after experimental stroke produces a structural/functional recovery in the brain which is correlated with an increase in activated brain glia and changes in circulating cytokines and growth factors. Stem cells therefore induce an important neuroprotective and/or regenerative response in the host organism.

【 授权许可】

Unknown   
© 2010 Cognizant Comm. Corp.

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