Pericytes Extend Survival of ALS SOD1 Mice and Induce the Expression of Antioxidant Enzymes in the Murine Model and in IPSCs Derived Neuronal Cells from an ALS Patient

Amyotrophic Lateral Sclerosis (ALS) is one of the most common adult-onset motor neuron disease causing a progressive, rapid and irreversible degeneration of motor neurons in the cortex, brain stem and spinal cord. No effective treatment is available and cell therapy clinical trials are currently bei...

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Published in:	Stem cell reviews Vol. 13; no. 5; pp. 686 - 698
Main Authors:	Coatti, Giuliana Castello, Frangini, Miriam, Valadares, Marcos C., Gomes, Juliana Plat, Lima, Natalia O., Cavaçana, Natale, Assoni, Amanda F., Pelatti, Mayra V., Birbrair, Alexander, de Lima, Antonio Carlos Pedroso, Singer, Julio M., Rocha, Francisco Marcelo M., Da Silva, Giovani Loiola, Mantovani, Mario Sergio, Macedo-Souza, Lucia Inês, Ferrari, Merari F. R., Zatz, Mayana
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-10-2017
Subjects:	Adipose Tissue - cytology Adipose Tissue - metabolism Amyotrophic Lateral Sclerosis - genetics Amyotrophic Lateral Sclerosis - mortality Amyotrophic Lateral Sclerosis - pathology Amyotrophic Lateral Sclerosis - therapy Animals Biomedical and Life Sciences Biomedical Engineering and Bioengineering Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology Brain Stem - metabolism Brain Stem - pathology Catalase - genetics Catalase - metabolism Cell Biology Cerebral Cortex - metabolism Cerebral Cortex - pathology Disease Models, Animal Female Gene Expression Humans Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Life Sciences Male Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - metabolism Mice Mice, Transgenic Motor Neurons - metabolism Motor Neurons - pathology Mutation Pericytes - cytology Pericytes - metabolism Pericytes - transplantation Regenerative Medicine/Tissue Engineering RNA-Binding Protein FUS - genetics RNA-Binding Protein FUS - metabolism Spinal Cord - metabolism Spinal Cord - pathology Stem Cells Superoxide Dismutase-1 - deficiency Superoxide Dismutase-1 - genetics Survival Analysis Pericytes Mesenchymal stromal cells Motor neurons Amyotrophic lateral sclerosis SOD1 mice IPSCs
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Summary:	Amyotrophic Lateral Sclerosis (ALS) is one of the most common adult-onset motor neuron disease causing a progressive, rapid and irreversible degeneration of motor neurons in the cortex, brain stem and spinal cord. No effective treatment is available and cell therapy clinical trials are currently being tested in ALS affected patients. It is well known that in ALS patients, approximately 50% of pericytes from the spinal cord barrier are lost. In the central nervous system, pericytes act in the formation and maintenance of the blood-brain barrier, a natural defense that slows the progression of symptoms in neurodegenerative diseases. Here we evaluated, for the first time, the therapeutic effect of human pericytes in vivo in SOD1 mice and in vitro in motor neurons and other neuronal cells derived from one ALS patient. Pericytes and mesenchymal stromal cells (MSCs) were derived from the same adipose tissue sample and were administered to SOD1 mice intraperitoneally. The effect of the two treatments was compared. Treatment with pericytes extended significantly animals survival in SOD1 males, but not in females that usually have a milder phenotype with higher survival rates. No significant differences were observed in the survival of mice treated with MSCs. Gene expression analysis in brain and spinal cord of end-stage animals showed that treatment with pericytes can stimulate the host antioxidant system. Additionally, pericytes induced the expression of SOD1 and CAT in motor neurons and other neuronal cells derived from one ALS patient carrying a mutation in FUS . Overall, treatment with pericytes was more effective than treatment with MSCs. Our results encourage further investigations and suggest that pericytes may be a good option for ALS treatment in the future. Graphical Abstract ᅟ
ISSN:	1550-8943 1558-6804 2629-3277
DOI:	10.1007/s12015-017-9752-2