Transplantation of bone marrow mononuclear cells prolongs survival, delays disease onset and progression and mitigates neuronal loss in pre-symptomatic, but not symptomatic ALS mice.
Cell-based therapy provides a novel strategy to restore lost neurons or modulate the degenerating microenvironment in amyotrophic lateral sclerosis (ALS). This study verified the therapeutic potential of bone marrow mononuclear cells (BMMCs) in SOD1G93Amice. BMMCs were obtained from enhanced green fluorescent protein (EGFP) transgenic C57BL/6 mice (EGFPBMMCs) or from SOD1G93Atransgenic mice (mSOD1BMMCs) and given to mice at the pre-symptomatic or late symptomatic stage. Survival, body weight and motor performance data were recorded. DNA integrity was evaluated using the alkaline comet assay. The spinal cords were collected to assess motoneuron preservation and cell migration.EGFPBMMCs andmSOD1BMMCs transplantation to pre-symptomatic SOD1G93Amice prolonged survival and delayed disease progression. The effects were more significant for theEGFPBMMC-transplanted mice. In late symptomatic mice,EGFPBMMCs promoted a discrete increase in survival, without other clinical improvements. DNA fromEGFPBMMCs andmSOD1BMMCs was found in the spinal cords of transplanted animals. DNA damage was not modified by BMMCs in any of the studied groups. Despite positive behavioral effects observed in our study, the limited results we observed for late transplanted mice call for caution before clinical application of BMMCs in ALS.
Centro de Pesquisa Pré-Clínica, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Porto Alegre, RS, Brazil; Laboratório de Neurociências, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
Gianina Teribele
GT
Venturin
Centro de Pesquisa Pré-Clínica, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Porto Alegre, RS, Brazil; Laboratório de Neurociências, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
Samuel
S
Greggio
Laboratório de Neurociências, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
Gabriele
G
Zanirati
Laboratório de Terapia Celular, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
Daniel Rodrigo
DR
Marinowic
Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Iuri Marques
IM
de Oliveira
Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
João Antonio
JA
Pêgas Henriques
Centro de Pesquisa Pré-Clínica, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Porto Alegre, RS, Brazil; Laboratório de Neurociências, Instituto do Cérebro do Rio Grande do Sul - Brain Institute (BraIns), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. Electronic address: jcc@pucrs.br.
Jaderson Costa
JC
DaCosta
D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016026:Bone Marrow Transplantation; D016923:Cell Death; D002470:Cell Survival; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics; D019076:Transgenes
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
Amyotrophic lateral sclerosis; Cell therapy; SOD1 mice