Safety and biodistribution of mesenchymal stromal/stem cells and biocompatible neurotrophin-releasing polyelectrolyte nanoparticles as a preclinical study in amyotrophic lateral sclerosis (ALS) cell therapy

Amyotrophic lateral sclerosis (ALS) is a multifactorial disease that complicates the identification of unique therapeutic targets. Stem cells and neurotrophins hold therapeutic promise due to their neuroprotective and anti-inflammatory roles. This study preclinically evaluated the safety of mesenchymal stem cells (MSCs) and neurotrophin-releasing polyelectrolyte nanoparticles (NTs) as potential adjuvant therapies in a porcine model. Four groups of castrated male pigs were used. Group I (control) received saline and pegylated NT3-BDNF nanoparticles. Group II received adipose-derived stem cells (ASCs), Group III Wharton’s jelly-derived MSCs (WJ-MSCs), each followed by NT3-BDNF nanoparticles, while Group IV underwent only spinal puncture. Treatments were administered intrathecally. Safety was assessed using MRI, hematological and biochemical parameters, and cerebrospinal fluid analysis. Cell localization was studied with iron-label staining, and tissue integrity was evaluated histologically. Biochemical tests revealed no significant blood parameter changes. C-reactive protein (CRP) levels decreased after NTs and NT–MSC combinations, indicating an anti-inflammatory effect. Biodistribution analysis showed MSC migration via cerebrospinal fluid and accumulation around the spinal cord and brain. MRI and behavioral monitoring confirmed the absence of adverse effects. These findings demonstrate that MSC therapy combined with neurotrophin-releasing nanoparticles is safe and feasible as adjunct therapy for ALS.