Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice
Summary: 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 ce...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Stem Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671117304915 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jack C. Reidling Aroa Relaño-Ginés Sandra M. Holley Joseph Ochaba Cindy Moore Brian Fury Alice Lau Andrew H. Tran Sylvia Yeung Delaram Salamati Chunni Zhu Asa Hatami Carlos Cepeda Joshua A. Barry Talia Kamdjou Alvin King Dane Coleal-Bergum Nicholas R. Franich Frank M. LaFerla Joan S. Steffan Mathew Blurton-Jones Charles K. Meshul Gerhard Bauer Michael S. Levine Marie-Francoise Chesselet Leslie M. Thompson |
| spellingShingle |
Jack C. Reidling Aroa Relaño-Ginés Sandra M. Holley Joseph Ochaba Cindy Moore Brian Fury Alice Lau Andrew H. Tran Sylvia Yeung Delaram Salamati Chunni Zhu Asa Hatami Carlos Cepeda Joshua A. Barry Talia Kamdjou Alvin King Dane Coleal-Bergum Nicholas R. Franich Frank M. LaFerla Joan S. Steffan Mathew Blurton-Jones Charles K. Meshul Gerhard Bauer Michael S. Levine Marie-Francoise Chesselet Leslie M. Thompson Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice Stem Cell Reports Huntington's disease neural stem cell transplantation R6/2 mice Q140 mice embryonic stem cells |
| author_facet |
Jack C. Reidling Aroa Relaño-Ginés Sandra M. Holley Joseph Ochaba Cindy Moore Brian Fury Alice Lau Andrew H. Tran Sylvia Yeung Delaram Salamati Chunni Zhu Asa Hatami Carlos Cepeda Joshua A. Barry Talia Kamdjou Alvin King Dane Coleal-Bergum Nicholas R. Franich Frank M. LaFerla Joan S. Steffan Mathew Blurton-Jones Charles K. Meshul Gerhard Bauer Michael S. Levine Marie-Francoise Chesselet Leslie M. Thompson |
| author_sort |
Jack C. Reidling |
| title |
Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice |
| title_short |
Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice |
| title_full |
Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice |
| title_fullStr |
Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice |
| title_full_unstemmed |
Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice |
| title_sort |
human neural stem cell transplantation rescues functional deficits in r6/2 and q140 huntington's disease mice |
| publisher |
Elsevier |
| series |
Stem Cell Reports |
| issn |
2213-6711 |
| publishDate |
2018-01-01 |
| description |
Summary: 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. |
| topic |
Huntington's disease neural stem cell transplantation R6/2 mice Q140 mice embryonic stem cells |
| url |
http://www.sciencedirect.com/science/article/pii/S2213671117304915 |
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doaj-6a20e0b98a194e96bbd0862727f88f6d2020-11-25T03:04:14ZengElsevierStem Cell Reports2213-67112018-01-01101587210.1016/j.stemcr.2017.11.005Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease MiceJack C. Reidling0Aroa Relaño-Ginés1Sandra M. Holley2Joseph Ochaba3Cindy Moore4Brian Fury5Alice Lau6Andrew H. Tran7Sylvia Yeung8Delaram Salamati9Chunni Zhu10Asa Hatami11Carlos Cepeda12Joshua A. Barry13Talia Kamdjou14Alvin King15Dane Coleal-Bergum16Nicholas R. Franich17Frank M. LaFerla18Joan S. Steffan19Mathew Blurton-Jones20Charles K. Meshul21Gerhard Bauer22Michael S. Levine23Marie-Francoise Chesselet24Leslie M. Thompson25Institute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USAIntellectual 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, USADepartment of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USAPortland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USAInstitute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USADepartment of Psychiatry & Human Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USAInstitute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USAInstitute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USAInstitute for Memory Impairment and Neurological Disorders, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USAIntellectual 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, USAIntellectual 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, USAIntellectual 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, USADepartment of Neurobiology & Behavior, University of California, Irvine, 3400 Biological Sciences III, Irvine, CA 92697-4545, USAInstitute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USAInstitute 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, USAInstitute 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, USAInstitute 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, USAPortland 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, USAInstitute for Regenerative Cures, University of California, Davis, 2921 Stockton Boulevard, Sacramento, CA 95817, USAIntellectual 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, USADepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USAInstitute 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2213671117304915Huntington's diseaseneural stem celltransplantationR6/2 miceQ140 miceembryonic stem cells |