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Chimerization of astroglial population in the lumbar spinal cord after mesenchymal stem cell transplantation prolongs survival in a rat model of amyotrophic lateral sclerosis.

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Boucherie, Cédric Schäfer, Sabrina [UCL] Lavand'homme, Patricia [UCL] Maloteaux, Jean-Marie [UCL] Hermans, Emmanuel [UCL]

Adult mesenchymal stem cells (MSCs) exhibit neuroprotective properties when introduced into the degenerating central nervous system through different putative mechanisms including secretion of growth factors and transdifferentiation. In the present study, we injected MSCs into the cerebrospinal fluid of symptomatic hSOD1(G93A) rats, a transgenic animal model of familial amyotrophic lateral sclerosis (ALS) expressing a mutated form of the human superoxide dismutase. MSCs were found to infiltrate the nervous parenchyma and migrate substantially into the ventral gray matter, where motor neurons degenerate. Even though overall astrogliosis was not modified, MSCs differentiated massively into astrocytes at the site of degeneration. The intrathecal delivery of MSCs and the subsequent generation of healthy astrocytes at symptomatic stage decreased motor neuron loss in the lumbar spinal cord, preserving motor functions and extending the survival of hSOD1(G93A) rats. This neuroprotection was correlated with decreased inflammation, as shown by the lower proliferation of microglial cells and the reduced expressiontion of COX-2 and NOX-2. Together, these data highlight the protective capacity of adult MSC-derived astrocytes when grafted into the central nervous system and illustrate an attractive strategy to target excessive inflammation in ALS. (c) 2009 Wiley-Liss, Inc.

Document type Article de périodique (Journal article) – Article de recherche – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2009
Language Anglais
Journal information "Journal of neuroscience research" - Vol. 87, no. 9, p. 2034-46 (2009)
Peer reviewed yes
Publisher Wiley Interscience (New-York)
issn 0360-4012
e-issn 1097-4547
Publication status Publié
Affiliations UCL - (SLuc) Service d'anesthésiologie
UCL - MD/FSIO - Département de physiologie et pharmacologie
UCL - MD/CHIR - Département de chirurgie
MESH Subject Survival Rate ; Superoxide Dismutase - genetics ; Spinal Cord - cytology - physiology - surgery ; Rats, Transgenic ; Rats, Sprague-Dawley ; Rats ; NADPH Oxidase - metabolism ; Microglia - physiology ; Mesenchymal Stem Cells - cytology - physiology ; Mesenchymal Stem Cell Transplantation - methods ; Membrane Glycoproteins - metabolism ; Male ; Humans ; Graft Survival - physiology ; Gliosis - physiopathology - prevention & control - surgery ; Disease Models, Animal ; Cyclooxygenase 2 - metabolism ; Chimera - physiology ; Cell Survival - physiology ; Cell Differentiation - physiology ; Cell Communication - physiology ; Astrocytes - cytology - physiology ; Animals ; Amyotrophic Lateral Sclerosis - physiopathology - surgery
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Bibliographic reference Boucherie, Cédric ; Schäfer, Sabrina ; Lavand'homme, Patricia ; Maloteaux, Jean-Marie ; Hermans, Emmanuel. Chimerization of astroglial population in the lumbar spinal cord after mesenchymal stem cell transplantation prolongs survival in a rat model of amyotrophic lateral sclerosis.. In: Journal of neuroscience research, Vol. 87, no. 9, p. 2034-46 (2009)
Permanent URL http://hdl.handle.net/2078.1/21872