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

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 SOD1 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.