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 SOD1 ^G93A mice. BMMCs were obtained from enhanced green fluorescent protein (EGFP) transgenic C57BL/6 mice ( ^EGFP BMMCs) or from SOD1 ^G93A transgenic mice ( ^mSOD1 BMMCs) 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. ^EGFP BMMCs and ^mSOD1 BMMCs transplantation to pre-symptomatic SOD1 ^G93A mice prolonged survival and delayed disease progression. The effects were more significant for the ^EGFP BMMC-transplanted mice. In late symptomatic mice, ^EGFP BMMCs promoted a discrete increase in survival, without other clinical improvements. DNA from ^EGFP BMMCs and ^mSOD1 BMMCs 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.
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