title: Intraspinal administration of human spinal cord-derived neural progenitor cells in the G93A-SOD1 mouse model of ALS delays symptom progression, prolongs survival and increases expression of endogenous neurotrophic factors.
abstract: Neural stem or progenitor cells are considered to be a novel therapeutic strategy for amyotrophic lateral sclerosis (ALS), based on their potential to generate a protective environment rather than to replace degenerating motor neurons. Following local injection to the spinal cord, neural progenitor cells may generate glial cells and release neurotrophic factors. In the present study, human spinal cord-derived neural progenitor cells (hscNPCs) were injected into the lumbar spinal cord of G93A-SOD1 ALS transgenic mice. We evaluated the potential effect of hscNPC treatment by survival analysis and behavioural/phenotypic assessments. Immunohistological and real-time PCR experiments were performed at a defined time point to study the underlying mechanisms. Symptom progression in hscNPC-injected mice was significantly delayed at the late stage of disease. On average, survival was only prolonged for 5 days. Animals treated with hscNPCs performed significantly better in motor function tests between weeks 18 and 19. Increased production of GDNF and IGF-1 mRNA was detectable in spinal cord tissue of hscNPC-treated mice. In summary, treatment with hscNPCs led to increased endogenous production of several growth factors and increased the preservation of innervated motor neurons but had only a small effect on overall survival. Copyright © 2015 John Wiley & Sons, Ltd.
authors: Department of Neurology, Hannover Medical School, Germany.
authors: Sarah
authors: S
authors: Knippenberg
authors: Department of Neurology, Hannover Medical School, Germany.|Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors: Klaus Jan
authors: KJ
authors: Rath
authors: Department of Neurology, Hannover Medical School, Germany.|Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors: Sebastian
authors: S
authors: Böselt
authors: Department of Neurology, Hannover Medical School, Germany.|Centre for Systems Neuroscience, Hannover, Germany.
authors: Nadine
authors: N
authors: Thau-Habermann
authors: German Centre for Neurodegenerative Diseases (DZNE), Technical University of Munich, Germany.
authors: Sigrid C
authors: SC
authors: Schwarz
authors: Department of Neurology, Hannover Medical School, Germany.|Centre for Systems Neuroscience, Hannover, Germany.
authors: Reinhard
authors: R
authors: Dengler
authors: Department of Neurology, Hannover Medical School, Germany.|Centre for Systems Neuroscience, Hannover, Germany.
authors: Florian
authors: F
authors: Wegner
authors: Department of Neurology, Hannover Medical School, Germany.|Centre for Systems Neuroscience, Hannover, Germany.|Integriertes Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
authors: Susanne
authors: S
authors: Petri
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D019070:Cell Lineage; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007278:Injections, Spinal; D008822:Mice, Transgenic; D009043:Motor Activity; D009414:Nerve Growth Factors / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D033581:Stem Cell Transplantation; D013482:Superoxide Dismutase / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D013482:Superoxide Dismutase
keywords: G93A-SOD1 mouse model; human neural progenitor cells; immunohistochemistry; intraspinal injection; motor function