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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
Author(s) -
Boucherie Cédric,
Schäfer Sabrina,
Lavand'homme Patricia,
Maloteaux JeanMarie,
Hermans Emmanuel
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22038
Subject(s) - astrogliosis , mesenchymal stem cell , neuroprotection , spinal cord , amyotrophic lateral sclerosis , central nervous system , population , pathology , transplantation , biology , lumbar spinal cord , spinal cord injury , neuroregeneration , medicine , neuroscience , disease , environmental health
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. © 2009 Wiley‐Liss, Inc.