Positive Effect of Transplantation of hNT Neurons (NTera 2/D1 Cell-Line) in a Model of Familial Amyotrophic Lateral Sclerosis

• Published in: Experimental neurology 2002-04, Vol.174 (2), p.169-180
• Main Authors: Garbuzova-Davis, Svitlana, Willing, Alison E., Milliken, Melissa, Saporta, Samuel, Zigova, Tanya, Cahill, David W., Sanberg, Paul R.
• Format: Article
• Language: English
• Subjects: Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - therapy; Animals; Anterior Horn Cells - pathology; behavior; Behavior, Animal; Biological and medical sciences; Cu/Zn superoxide dismutase; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Disease Progression; Embryonal Carcinoma Stem Cells; familial amyotrophic lateral sclerosis; Graft Survival; hNT Neurons; Humans; Immunohistochemistry; Male; Medical sciences; Mice; Motor Activity; Neoplastic Stem Cells - transplantation; Neurology; Neurons - transplantation; Neurosurgery; Skull, brain, vascular surgery; Spinal Cord - cytology; Spinal Cord - pathology; Superoxide Dismutase - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Survival Rate; transgenic mice; transplantation; Transplantation, Heterologous; Treatment Outcome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2002.7860

Transplantation of hNT Neurons derived from the human teratocarcinoma cell-line (NTera2/D1) has been shown to ameliorate motor dysfunction in a number of injury or disease models in which the deficits are fairly localized. However, these cells have not been used before in a model with more extensive neurodegeneration. The aim of this study is to determine the effects of hNT Neuron transplants on motor neuron function in a mouse model of familial amyotrophic lateral sclerosis (FALS) in which there is a substitution of Alanine for Glycine at position 93 of the human SOD1 gene (G93A). Amyotrophic lateral sclerosis is a fatal degenerative motor neuron disease affecting the spinal cord, brainstem, and cortex. This disease clinically manifests as progressive muscular weakness and atrophy, leading to paralysis and death within 3–5 years of diagnosis. The FALS represents 10–13% of all cases. A range of behavioral tests was used to examine spontaneous locomotor activity, coordination, and muscle strength of mice. Long-term (10–11 weeks) transplantation of hNT Neurons into the L4–L5 segments of the ventral horn spinal cord of FALSG93A mice at 7 weeks of age (before onset of overt behavioral symptoms of disease) delayed the onset of motor dysfunction for at least 3 weeks. The average lifespan of the transplanted mice was 128 days compared to 106 days for media-injected group. The last mouse in the hNT Neuron transplanted group was euthanized at 135 days of age when it display partial paralysis of the hindlimbs. Immunohistochemical analysis of the implanted spinal cords demonstrated the survival of grafted hNT Neurons and showed many healthy-appearing motor neurons near the implant site. These results suggest that hNT Neuron transplantation may be a promising therapeutic strategy for ALS.