Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21736505
DOI
10.3109/14653249.2011.592521
PII: S1465-3249(11)70585-0
Knihovny.cz E-resources
- MeSH
- Amyotrophic Lateral Sclerosis genetics pathology physiopathology therapy MeSH
- Apoptosis genetics MeSH
- Animals, Genetically Modified MeSH
- Rats MeSH
- Humans MeSH
- Mesenchymal Stem Cells metabolism pathology MeSH
- Spinal Cord metabolism pathology MeSH
- Disease Models, Animal MeSH
- Motor Neurons immunology metabolism pathology MeSH
- Cell Movement MeSH
- Motor Activity MeSH
- Superoxide Dismutase-1 MeSH
- Superoxide Dismutase genetics MeSH
- Mesenchymal Stem Cell Transplantation * MeSH
- Cell Survival MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- SOD1 protein, human MeSH Browser
- Sod1 protein, rat MeSH Browser
- Superoxide Dismutase-1 MeSH
- Superoxide Dismutase MeSH
BACKGROUND AIMS: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of brain and spinal cord motor neurons (MN). The intraspinal and systemic grafting of mesenchymal stromal cells (MSC) was used to treat symptomatic transgenic rats overexpressing human superoxide dismutase 1 (SOD1) in order to alleviate the disease course and prolong the animals' lifespan. METHODS: At the age of 16 weeks (disease onset) the rats received two grafts of MSC expressing green fluorescent protein (GFP(+) MSC) on the same day, intraspinally (10(5) cells) and intravenously (2 × 10(6) cells). Sham-treated animals were injected with phosphate-buffered saline (PBS). Motor activity, grip strength and body weight were tested, followed by immunohistochemical analysis. RESULTS: The combined grafting of MSC into symptomatic rats had a significant effect on motor activity and grip strength starting 4 weeks after transplantation. The lifespan of animals in the treated group was 190 ± 3.33 days compared with 179 ± 3.6 days in the control group of animals. Treated rats had a larger number of MN at the thoracic and lumbar levels; these MN were of larger size, and the intensity of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining in the somas of apoptotic MN at the thoracic level was much lower than in sham-treated animals. Transplanted GFP(+) MSC survived in the spinal cord until the end stage of the disease and migrated both rostrally and caudally from the injection site. CONCLUSIONS: Intraspinal and intravenous transplantation of MSC has a beneficial and possibly synergistic effect on the lifespan of ALS animals.
References provided by Crossref.org
Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis
Neuroprotective Potential of Cell-Based Therapies in ALS: From Bench to Bedside
Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer's Disease
Stem cells in regenerative medicine
Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury
