摘要:SummarySeveral treatments have been attempted in amyotrophic lateral sclerosis (ALS) animal models and patients. Recently, transplantation of bone marrow-derived mononuclear cells (MNCs) was investigated as a regenerative therapy for ALS, but satisfactory treatments remain to be established. To develop an effective treatment, we focused on mesenchymal stem cells (MSCs) expressing hepatocyte growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor using human artificial chromosome vector (HAC-MSCs). Here, we demonstrated the transplantation of MNCs with HAC-MSCs in ALS mice. As per our results, the progression of motor dysfunction was significantly delayed, and their survival was prolonged dramatically. Additional analysis revealed preservation of motor neurons, suppression of gliosis, engraftment of numerous MNCs, and elevated chemotaxis-related cytokines in the spinal cord of treated mice. Therefore, growth factor-expressing MSCs enhance the therapeutic effects of bone marrow-derived MNCs for ALS and have a high potential as a novel cell therapy for patients with ALS.Graphical AbstractDisplay OmittedHighlights•MNCs with growth factor-expressing MSCs is an effective cell therapy for ALS mice•The MSCs enhance therapeutic effects by migration of MNCs into ALS mice spinal cord•This cell therapy suppresses neuronal loss and gliosis in ALS mice spinal cord•This cell therapy induces several cytokines expression in ALS mice spinal cordMolecular Neuroscience; Cellular Neuroscience; Stem Cells Research