Chimerization of astroglial population in the lumbar spinal cord after mesenchymal stem cell transplantation prolongs survival in a rat model of amyotrophic lateral sclerosis.
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.
Boucherie
Cédric
C
Institute of Neuroscience (INES), Université catholique de Louvain, Brussels, Belgium.
Schäfer
Sabrina
S
Lavand'homme
Patricia
P
Maloteaux
Jean-Marie
JM
Hermans
Emmanuel
E
D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002678:Chimera / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005911:Gliosis / Q000503:physiopathology / Q000517:prevention & control / Q000601:surgery; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D017628:Microglia / Q000502:physiology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015996:Survival Rate
D008562:Membrane Glycoproteins; C000606290:SOD1 protein, human; D051546:Cyclooxygenase 2; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases