title: Mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  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.
authors: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors: Serhiy
authors: S
authors: Forostyak
authors: Pavla
authors: P
authors: Jendelova
authors: Miroslava
authors: M
authors: Kapcalova
authors: David
authors: D
authors: Arboleda
authors: Eva
authors: E
authors: Sykova
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009043:Motor Activity; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1