Mesenchymal stromal/stem cells for neurological disorders in humans: an evidence-mapped clinical review.

Mesenchymal stromal/stem cells (MSCs) have been tested clinically across a wide spectrum of neurological disorders, motivated by their immunomodulatory and trophic ("bystander") mechanisms rather than durable neural replacement. Here, we synthesize human prospective clinical trials that administered MSC products for neurological indications, prioritizing study design/goals, disease stage/severity, cell source/manufacturing, dose/route, detailed clinical assessments, quantified score changes, and adverse events (AEs). Across indications, trials frequently demonstrate feasibility and short-term safety, while efficacy signals are heterogeneous and strongly dependent on disease stage and endpoint selection criteria. The most methodologically rigorous signals with quantified motor outcomes include stereotactic intracerebral implantation of SB623 for chronic motor deficits after traumatic brain injury (TBI). In amyotrophic lateral sclerosis (ALS), randomized evidence supports safety and early slope-based signals in selected subgroups after intrathecal MSC regimens, but durable clinical benefit remains unproven. In hypoxic-ischemic encephalopathy (HIE), controlled data suggest functional improvements in small cohorts, and neonatal studies support feasibility adjunctive to hypothermia. We highlight design features most likely to de-risk efficacy interpretation: adequately powered randomized controlled trials, disease-stage stratification, prespecified clinically meaningful change thresholds, standardized rehabilitation co-interventions, and transparent AE adjudication.