Bone-marrow mononuclear cell therapy in a mouse model of amyotrophic lateral sclerosis: Functional outcomes from different administration routes

•BMMC IV therapy had no significant effects on ALS animal’s motor performance or survival.•BMMC IM therapy had no significant effects on ALS animal’s motor performance or survival.•BMMC IV + IM therapy delayed disease progression, decreased microgliosis and protected NMJ. Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1G93A model of ALS. BMMCs were isolated from non-transgenic, age matched animals and administered intravenously (IV), intramuscularly (IM), and intravenously and intramuscular concomitantly (IV + IM). BMMC therapy had no significant beneficial effects when injected IV or IM, but delayed disease progression when these two routes were used concomitantly. BMMC IV + IM treatment reduced the number of microglia cells in the spinal cord and partially protected of neuromuscular-junction innervation, but had no effect in preventing motor-neuron loss. This study showed that injection of BMMC IV + IM had better results when compared to each route in isolation, highlighting the importance of targeting multiple anatomical regions in the treatment of ALS.