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

• Published in: Neuroscience letters 2016-10, Vol.633, p.182-188
• Main Authors: Venturin, Gianina Teribele, Greggio, Samuel, Zanirati, Gabriele, Marinowic, Daniel Rodrigo, de Oliveira, Iuri Marques, Pêgas Henriques, João Antonio, DaCosta, Jaderson Costa
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - mortality; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - therapy; Animals; Bone Marrow Transplantation; Cell Death; Cell Survival; Cell therapy; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Male; Mice, Transgenic; Motor Neurons - pathology; Neurons - pathology; SOD1 mice; Superoxide Dismutase - genetics; Transgenes
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.09.030

•We investigate the effect of bone marrow mononuclear cells (BMMC) in ALS mice.•Pre-symptomatic BMMC transplantation improves the animal’s clinical condition.•Only non-mSOD1 BMMC are beneficial in late symptomatic animals.•Early administration of BMMC promotes better outcomes. 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 SOD1G93A mice. BMMCs were obtained from enhanced green fluorescent protein (EGFP) transgenic C57BL/6 mice (EGFPBMMCs) or from SOD1G93A transgenic 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 and mSOD1BMMCs transplantation to pre-symptomatic SOD1G93A mice prolonged survival and delayed disease progression. The effects were more significant for the EGFPBMMC-transplanted mice. In late symptomatic mice, EGFPBMMCs promoted a discrete increase in survival, without other clinical improvements. DNA from EGFPBMMCs and mSOD1BMMCs 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.