Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis

• Published in: Neurobiology of disease Vol. 31; no. 3; pp. 395 - 405
• Main Authors: Vercelli, A, Mereuta, O.M, Garbossa, D, Muraca, G, Mareschi, K, Rustichelli, D, Ferrero, I, Mazzini, L, Madon, E, Fagioli, F
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2008; Elsevier
• Subjects: Amyotrophic Lateral Sclerosis - physiopathology; Amyotrophic Lateral Sclerosis - therapy; Animals; Astrocyte; Astrocytes - cytology; Astrocytes - metabolism; Cell Survival - physiology; Cell therapy; Disease Models, Animal; Female; Gliosis - metabolism; Gliosis - physiopathology; Gliosis - surgery; Humans; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Mice; Microglia; Microglia - cytology; Microglia - metabolism; Motoneuron; Motor Neurons - pathology; Movement Disorders - etiology; Movement Disorders - physiopathology; Movement Disorders - surgery; Mutation - genetics; Myelitis - physiopathology; Myelitis - therapy; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Nerve Degeneration - surgery; Neurology; Neuroprotection; Recovery of Function - physiology; Sex Characteristics; SOD1; Spinal Cord - pathology; Spinal Cord - physiopathology; Spinal Cord - surgery; Superoxide Dismutase - genetics; Superoxide Dismutase-1; Survival Rate; Treatment Outcome; Neuroprotection; Motoneuron; Cell therapy; Astrocyte; SOD1; Microglia
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2008.05.016

Abstract Amyotrophic lateral sclerosis (ALS) is a lethal disease affecting motoneurons. In familial ALS, patients bear mutations in the superoxide dismutase gene (SOD1). We transplanted human bone marrow mesenchymal stem cells (hMSCs) into the lumbar spinal cord of asymptomatic SOD1G93A mice, an experimental model of ALS. hMSCs were found in the spinal cord 10 weeks after, sometimes close to motoneurons and were rarely GFAP- or MAP2-positive. In females, where progression is slower than in males, astrogliosis and microglial activation were reduced and motoneuron counts with the optical fractionator were higher following transplantation. Motor tests (Rotarod, Paw Grip Endurance, neurological examination) were significantly improved in transplanted males. Therefore hMSCs are a good candidate for ALS cell therapy: they can survive and migrate after transplantation in the lumbar spinal cord, where they prevent astrogliosis and microglial activation and delay ALS-related decrease in the number of motoneurons, thus resulting in amelioration of the motor performance.