PMID- 29233555 OWN - NLM STAT- MEDLINE DCOM- 20181226 LR - 20210109 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 10 IP - 1 DP - 2018 Jan 9 TI - Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice. PG - 58-72 LID - S2213-6711(17)30491-5 [pii] LID - 10.1016/j.stemcr.2017.11.005 [doi] AB - 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. CI - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Reidling, Jack C AU - Reidling JC AD - Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Relano-Gines, Aroa AU - Relano-Gines A AD - Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. FAU - Holley, Sandra M AU - Holley SM AD - 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. FAU - Ochaba, Joseph AU - Ochaba J AD - Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Moore, Cindy AU - Moore C AD - Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA. FAU - Fury, Brian AU - Fury B AD - Institute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USA. FAU - Lau, Alice AU - Lau A AD - Department of Psychiatry & Human Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Tran, Andrew H AU - Tran AH AD - Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Yeung, Sylvia AU - Yeung S AD - Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Salamati, Delaram AU - Salamati D AD - Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Zhu, Chunni AU - Zhu C AD - Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. FAU - Hatami, Asa AU - Hatami A AD - Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. FAU - Cepeda, Carlos AU - Cepeda C AD - 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. FAU - Barry, Joshua A AU - Barry JA AD - 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. FAU - Kamdjou, Talia AU - Kamdjou T AD - 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. FAU - King, Alvin AU - King A AD - Department of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA. FAU - Coleal-Bergum, Dane AU - Coleal-Bergum D AD - Institute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USA. FAU - Franich, Nicholas R AU - Franich NR AD - Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. FAU - LaFerla, Frank M AU - LaFerla FM AD - 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. FAU - Steffan, Joan S AU - Steffan JS AD - 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. FAU - Blurton-Jones, Mathew AU - Blurton-Jones M AD - 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 Gross Stem Cell Center, University of California, Irvine, Gross Hall, Room 3219, 845 Health Sciences Road, Irvine, CA 92697, USA. FAU - Meshul, Charles K AU - Meshul CK AD - 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. FAU - Bauer, Gerhard AU - Bauer G AD - Institute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USA. FAU - Levine, Michael S AU - Levine MS AD - 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, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA. FAU - Chesselet, Marie-Francoise AU - Chesselet MF AD - Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. FAU - Thompson, Leslie M AU - Thompson LM AD - 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 Psychiatry & Human Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USA; Sue and Bill Gross Stem Cell Center, University of California, Irvine, Gross Hall, Room 3219, 845 Health Sciences Road, Irvine, CA 92697, USA. Electronic address: lmthomps@uci.edu. LA - eng GR - R01 NS041574/NS/NINDS NIH HHS/United States GR - R56 NS090390/NS/NINDS NIH HHS/United States GR - I01 BX000552/BX/BLRD VA/United States GR - I01 BX001643/BX/BLRD VA/United States GR - P30 CA062203/CA/NCI NIH HHS/United States GR - R01 NS090390/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20171207 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 SB - IM MH - Animals MH - Cell Line MH - *Cognition MH - Disease Models, Animal MH - Heterografts MH - Human Embryonic Stem Cells/metabolism/pathology MH - Humans MH - Huntington Disease/metabolism/pathology/physiopathology/*therapy MH - Mice MH - *Motor Activity MH - Neural Stem Cells/metabolism/pathology/*transplantation MH - *Recovery of Function PMC - PMC5768890 OTO - NOTNLM OT - Huntington's disease OT - Q140 mice OT - R6/2 mice OT - embryonic stem cells OT - neural stem cell OT - transplantation EDAT- 2017/12/14 06:00 MHDA- 2018/12/27 06:00 PMCR- 2017/12/07 CRDT- 2017/12/14 06:00 PHST- 2017/03/03 00:00 [received] PHST- 2017/11/03 00:00 [revised] PHST- 2017/11/03 00:00 [accepted] PHST- 2017/12/14 06:00 [pubmed] PHST- 2018/12/27 06:00 [medline] PHST- 2017/12/14 06:00 [entrez] PHST- 2017/12/07 00:00 [pmc-release] AID - S2213-6711(17)30491-5 [pii] AID - 10.1016/j.stemcr.2017.11.005 [doi] PST - ppublish SO - Stem Cell Reports. 2018 Jan 9;10(1):58-72. doi: 10.1016/j.stemcr.2017.11.005. Epub 2017 Dec 7.