This study evaluates the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). A phase 1/2 open-safety clinical trial was conducted, enrolling 15 MS patients and 19 ALS patients. MSCs were injected intrathecally and intravenously, with 9 patients receiving magnetically labeled MSCs for tracking. The main outcome measure was the recording of side effects, with follow-up including adverse events evaluation, neurological disability assessment, magnetic resonance imaging, and immunological tests. No major adverse effects were reported, and the mean ALSFRS score remained stable in ALS patients. In MS patients, the mean EDSS score improved from 6.7 to 5.9 over 6 months. MRI visualized MSCs in the ventricles and spinal cord, and immunological analysis showed increased regulatory T cells and decreased lymphocyte proliferation. The study concludes that MSC transplantation is a clinically feasible and relatively safe procedure, inducing immediate immunomodulatory effects in MS and ALS patients.This study evaluates the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). A phase 1/2 open-safety clinical trial was conducted, enrolling 15 MS patients and 19 ALS patients. MSCs were injected intrathecally and intravenously, with 9 patients receiving magnetically labeled MSCs for tracking. The main outcome measure was the recording of side effects, with follow-up including adverse events evaluation, neurological disability assessment, magnetic resonance imaging, and immunological tests. No major adverse effects were reported, and the mean ALSFRS score remained stable in ALS patients. In MS patients, the mean EDSS score improved from 6.7 to 5.9 over 6 months. MRI visualized MSCs in the ventricles and spinal cord, and immunological analysis showed increased regulatory T cells and decreased lymphocyte proliferation. The study concludes that MSC transplantation is a clinically feasible and relatively safe procedure, inducing immediate immunomodulatory effects in MS and ALS patients.