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
| Autor: | Sarah, Knippenberg, Klaus Jan, Rath, Sebastian, Böselt, Nadine, Thau-Habermann, Sigrid C, Schwarz, Reinhard, Dengler, Florian, Wegner, Susanne, Petri |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
metabolism [Nerve Growth Factors]
transplantation [Neural Stem Cells] Mice Transgenic Motor Activity metabolism [RNA Messenger] genetics [RNA Messenger] Neural Stem Cells genetics [Superoxide Dismutase] Animals Humans therapy [Amyotrophic Lateral Sclerosis] Cell Lineage ddc:610 Nerve Growth Factors RNA Messenger cytology [Neural Stem Cells] pathology [Amyotrophic Lateral Sclerosis] Injections Spinal Superoxide Dismutase cytology [Spinal Cord] Amyotrophic Lateral Sclerosis physiopathology [Amyotrophic Lateral Sclerosis] Survival Analysis Disease Models Animal Spinal Cord Disease Progression Stem Cell Transplantation |
| Zdroj: | Journal of tissue engineering and regenerative medicine 11(3), 751-764 (2015). doi:10.1002/term.1972 |
| DOI: | 10.1002/term.1972 |
| Popis: | 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 WileySons, Ltd. |
| Databáze: | OpenAIRE |
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