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Immune Effects of Mesenchymal Stromal Cells in Experimental Stroke
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Immune Effects of Mesenchymal Stromal Cells in Experimental Stroke
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Journal Article
Immune Effects of Mesenchymal Stromal Cells in Experimental Stroke
2012
Overview
Preclinical trials confirmed the potential of mesenchymal stromal cells (MSCs) to improve functional recovery after experimental stroke. Beneficial effects of MSCs are often attributed to their immunosuppressive/immunomodulatory functions. Surprisingly, the influence of MSCs on the immune system after stroke is poorly understood, but requires special consideration because cerebral ischemia is associated with stroke-induced immunodepression that predisposes to bacterial infections with increased mortality. In this study, we intravenously transplanted syngeneic murine bone marrow-derived MSCs (mMSCs) into C57BL/6 mice at 6 hours after transient middle cerebral artery occlusion (MCAo; 60 minutes) to investigate the impact of MSCs on stroke-induced immunodepression. Transplantation of syngeneic splenocytes or phosphate-buffered saline (PBS) served as controls. An immune status was determined by flow cytometry on days 3 and 14 after MCAo, which did not reveal any negative effects of cell transplantation on stroke-induced immunodepression. Although our mMSCs were found to exert immunosuppressive effects in vitro, stroke-mediated immune cell dysfunction was not altered by mMSCs in ex-vivo stimulation assays with lipopolysaccharide or concanavalin A. Moreover, systemic inflammatory cytokine levels (interleukin-6, tumor necrosis factorα, interferonγ, monocyte chemoattractant protein-1) remained unchanged in the sera of mice after cerebral ischemia and cell transplantation. These results reduce safety concerns about MSC administration in ongoing clinical stroke trials.
Publisher
SAGE Publications,Nature Publishing Group,Sage Publications Ltd
Subject
/ Biological and medical sciences
/ Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
/ Ischemia
/ Leukocytes, Mononuclear - cytology
/ Leukocytes, Mononuclear - immunology
/ Male
/ Mesenchymal Stem Cell Transplantation
/ Mesenchymal Stromal Cells - immunology
/ Mice
/ Monocyte chemoattractant protein 1
/ Nervous system (semeiology, syndromes)
/ Original
/ Stroke
/ Vascular diseases and vascular malformations of the nervous system
