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Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice.
Reidling, Jack C; Relaño-Ginés, Aroa; Holley, Sandra M; Ochaba, Joseph; Moore, Cindy; Fury, Brian; Lau, Alice; Tran, Andrew H; Yeung, Sylvia; Salamati, Delaram; Zhu, Chunni; Hatami, Asa; Cepeda, Carlos; Barry, Joshua A; Kamdjou, Talia; King, Alvin; Coleal-Bergum, Dane; Franich, Nicholas R; LaFerla, Frank M; Steffan, Joan S; Blurton-Jones, Mathew; Meshul, Charles K; Bauer, Gerhard; Levine, Michael S; Chesselet, Marie-Francoise; Thompson, Leslie M.
Afiliación
  • Reidling JC; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Relaño-Ginés A; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
  • Holley SM; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
  • Ochaba J; Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Moore C; Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA.
  • Fury B; Institute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USA.
  • Lau A; Department of Psychiatry & Human Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Tran AH; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Yeung S; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Salamati D; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Zhu C; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
  • Hatami A; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
  • Cepeda C; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
  • Barry JA; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
  • Kamdjou T; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
  • King A; Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Coleal-Bergum D; Institute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USA.
  • Franich NR; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
  • LaFerla FM; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Steffan JS; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Department of Psychiatry & Human Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA.
  • Blurton-Jones M; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Sue and Bill
  • Meshul CK; Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA; Oregon Health & Science University, Department of Behavioral Neuroscience, 3181 SW Sam Jackson Park Road, L470, Portland, OR 97239, USA.
  • Bauer G; Institute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USA.
  • Levine MS; Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, Univers
  • Chesselet MF; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
  • Thompson LM; Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Department of
Stem Cell Reports ; 10(1): 58-72, 2018 01 09.
Article en En | MEDLINE | ID: mdl-29233555
Huntington's disease (HD) is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT) gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP)-grade human embryonic stem cell-derived neural stem cell (hNSC) line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF) in both models. These findings hold promise for future development of stem cell-based therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Cognición / Recuperación de la Función / Células-Madre Neurales / Actividad Motora Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Stem Cell Reports Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Cognición / Recuperación de la Función / Células-Madre Neurales / Actividad Motora Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Stem Cell Reports Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos