title: Intraspinal bone-marrow cell therapy at pre- and symptomatic phases in a mouse model of amyotrophic lateral sclerosis.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that selectively affects the motor neurons. The details of the mechanisms of selective motor-neuron death remain unknown and no effective therapy has been developed. We investigated the therapy with bone-marrow mononuclear cells (BMMC) in a mouse model of ALS (SOD1(G93A) mice).
  
  
  METHODS
  We injected 10(6) BMMC into the lumbar portion of the spinal cord of SOD1(G93A) mice in presymptomatic (9 weeks old) and symptomatic (14 weeks old) phases. In each condition, we analyzed the progression of disease and the lifespan of the animals.
  
  
  RESULTS
  We observed a mild transitory delay in the disease progression in the animals injected with BMMC in the presymptomatic phase. However, we observed no increase in the lifespan. When we injected BMMC in the symptomatic phase, we observed no difference in the animals' lifespan or in the disease progression. Immunohistochemistry for NeuN showed a decrease in the number of motor neurons during the course of the disease, and this decrease was not affected by either treatment. Using different strategies to track the BMMC, we noted that few cells remained in the spinal cord after transplantation. This observation could explain why the BMMC therapy had only a transitory effect.
  
  
  CONCLUSIONS
  This is the first report of intraspinal BMMC therapy in a mouse model of ALS. We conclude this cellular therapy has only a mild transitory effect when performed in the presymptomatic phase of the disease.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil. fegubert@biof.ufrj.br.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Gubert
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Decotelli
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Igor
authors.initials: I
authors.lastname: Bonacossa-Pereira
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Figueiredo
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation, Avenida Brasil 4365, Maguinhos, RJ 21040-900, Rio de Janeiro, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Zaverucha-do-Valle
authors.affiliation: Institute of Biomedical Sciences and National Center of Structural Biology and Bioimaging, CENABIO, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.|Instituto D'Or de Pesquisa e Educação (IDOR), Rua Diniz Cordeiro 30, Botafogo, RJ 22281-100, Rio de Janeiro, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tovar-Moll
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Luísa
authors.initials: L
authors.lastname: Hoffmann
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Turan P
authors.initials: TP
authors.lastname: Urmenyi
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Santiago
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Sala G2-028, Universidade Federal do Rio de Janeiro, Cidade Universitária, RJ 21941-902, Rio de Janeiro, Brazil.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Mendez-Otero
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D000870:Anterior Horn Cells / Q000502:physiology; D058070:Asymptomatic Diseases / Q000628:therapy*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002470:Cell Survival; D058948:Cell Tracking; D005260:Female; D007278:Injections, Spinal; D008161:Lumbosacral Region / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology; D009043:Motor Activity; D020125:Mutation, Missense; D020127:Recovery of Function; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Bone marrow cell therapy; Neuronal degeneration