Evidence map›Paper›PMID 37807512›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

Transplanted human neural stem cells rescue phenotypes in zQ175 Huntington's disease mice and innervate the striatum.

Sandra M Holley, Jack C Reidling, Carlos Cepeda, Jie Wu, Ryan G Lim, Alice Lau, Cindy Moore, Ricardo Miramontes, Brian Fury, Iliana Orellana and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Wrap it up: myelination of transplanted neurons for repair.Frontiers in cellular neuroscience · 2025
    Review
  7. Review
  8. Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024
    Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Sandra M HolleyIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Jack C ReidlingInstitute for Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
Carlos CepedaIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Jie WuDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Ryan G LimInstitute for Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
Alice LauPsychiatry & Human Behavior, University of California Irvine, Irvine, CA 92697, USA.
Cindy MoorePortland VA Medical Center, Portland, OR 97239, USA.
Ricardo MiramontesInstitute for Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
Brian FuryInstitute for Regenerative Cures, University of California Davis, Sacramento, CA 95817, USA.
Iliana OrellanaInstitute for Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
Michael NeelDepartment of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Dane Coleal-BergumInstitute for Regenerative Cures, University of California Davis, Sacramento, CA 95817, USA.
Edwin S MonukiDepartment of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Center, University of California Irvine, Irvine, CA 92697, USA.
Gerhard BauerInstitute for Regenerative Cures, University of California Davis, Sacramento, CA 95817, USA.
Charles K MeshulPortland VA Medical Center, Portland, OR 97239, USA; Oregon Health & Science University, Department of Behavioral Neuroscience and Pathology, Portland, OR 97239, USA.
Michael S LevineIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Leslie M ThompsonInstitute for Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Psychiatry & Human Behavior, University of California Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Center, University of California Irvine, Irvine, CA 92697, USA; Department of Neurobiology & Behavior University of California Irvine, Irvine, CA 92697, USA. Electronic address: lmthomps@uci.edu.

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Using Technology to Enhance Cancer Communication and Improve Clinical OutcomesP50CA095817 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI GUSTAFSON, DAVID H · 2003 to 2012
$19.3M
UCLA Center for Translational Research in Neurodevelopment: UC-TRaNU54HD087101 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCCRACKEN, JAMES T. · 2016 to 2020
$6.5M
Cortical Pathophysiology in Mouse Models of Huntington's DiseaseR01NS096994 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEVINE, MICHAEL S. · 2017 to 2020
$2.0M
Cortical Pathophysiology in Mouse Models of Huntington's DiseaseR56NS096994 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEVINE, MICHAEL S. · 2016 to 2016
$535k
NCI NIH HHS P30 CA062203NCI NIH HHS P50 CA095817NICHD NIH HHS U54 HD087101NINDS NIH HHS R01 NS096994NINDS NIH HHS R56 NS096994
6 · The paper itself

Abstract

Huntington's disease (HD), a genetic neurodegenerative disorder, primarily affects the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that, with short-term hNSC transplantation into the striatum of HD R6/2 mice, human cells differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here, we show that long-term (8 months) implantation of hNSCs into the striatum of HD zQ175 mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) levels, and reduces mutant huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry, single-nucleus RNA sequencing (RNA-seq), and electron microscopy demonstrate that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells, and form connections. Single-nucleus RNA-seq analysis also shows restoration of several mHTT-mediated transcriptional changes of endogenous striatal HD mouse cells. Remarkably, engrafted cells receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.

Indexed as

Huntington DiseaseNeural Stem CellsAnimalsCorpus StriatumDisease Models, AnimalHumansHuntingtin ProteinMiceMice, TransgenicNeuronsPhenotypeHuntingtin ProteinBDNFelectron microscopyelectrophysiologyHuntington’s diseaseneural stem cellssingle-nucleus RNA-seqstem cellszQ175 mice

Identifiers

PMID37807512
PMCPMC10727970

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.