Amyotrophic lateral sclerosis (ALS) involves progressive loss of upper and lower motor neurons, leading to paralysis and death within 5-year post-onset. To test if motor neuron progenitors (MNPs) are prospective for rescuing motor function in ALS patients, we derived MNPs from human bone marrow stromal cells (hBMSCs) and used SOD1G93A mutant mice to model ALS. The hBMSC-MNPs were transplanted to (i) the lateral ventricles of neonates (postnatal day 8) or (ii) the spinal cords of adults (P50-60). In the neonatal model, the hBMSC-MNPs survived in the cerebral cortex and extended axonal fibers into the spinal cord. In the adult model, the hBMSC-MNPs differentiated into ChAT+ lower motor neurons. Microglia counts significantly declined in both treated groups versus the vehicle controls; microglia morphology in the treated groups were indicative of the resting state, suggesting that inflammation had subsided. Rotarod and wire-hanging test results of the treated group in both models indicated preserved motor functions until the endpoint. The lifespans of all treated groups were extended beyond those of the controls. Altogether, our results indicate translational potential of hBMSC-MNPs in cell-based therapy for ALS patients.