Stem Cell-Derived Human Striatal Progenitors Innervate Striatal Targets and Alleviate Sensorimotor Deficit in a Rat Model of Huntington Disease.
Animals
Cells, Cultured
Corpus Striatum
/ cytology
Human Embryonic Stem Cells
/ cytology
Humans
Huntington Disease
/ therapy
Locomotion
Male
Neural Stem Cells
/ cytology
Neurogenesis
Rats
Regeneration
Sensation
Stem Cell Transplantation
/ methods
Substantia Nigra
/ cytology
Subthalamic Nucleus
/ cytology
Synapses
/ metabolism
Huntington disease
behavioral assessment
brain graft integration
cell replacement therapy
cell transplantation
human embryonic stem cells
medium spiny neurons
rabies virus-based synaptic tracing
regenerative medicine
striatum
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
12 05 2020
12 05 2020
Historique:
received:
21
10
2019
revised:
17
03
2020
accepted:
18
03
2020
pubmed:
18
4
2020
medline:
17
4
2021
entrez:
18
4
2020
Statut:
ppublish
Résumé
Huntington disease (HD) is an inherited late-onset neurological disorder characterized by progressive neuronal loss and disruption of cortical and basal ganglia circuits. Cell replacement using human embryonic stem cells may offer the opportunity to repair the damaged circuits and significantly ameliorate disease conditions. Here, we showed that in-vitro-differentiated human striatal progenitors undergo maturation and integrate into host circuits upon intra-striatal transplantation in a rat model of HD. By combining graft-specific immunohistochemistry, rabies virus-mediated synaptic tracing, and ex vivo electrophysiology, we showed that grafts can extend projections to the appropriate target structures, including the globus pallidus, the subthalamic nucleus, and the substantia nigra, and receive synaptic contact from both host and graft cells with 6.6 ± 1.6 inputs cell per transplanted neuron. We have also shown that transplants elicited a significant improvement in sensory-motor tasks up to 2 months post-transplant further supporting the therapeutic potential of this approach.
Identifiants
pubmed: 32302555
pii: S2213-6711(20)30108-9
doi: 10.1016/j.stemcr.2020.03.018
pmc: PMC7220987
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
876-891Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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