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Stem Cell-Derived Human Striatal Progenitors Innervate Striatal Targets and Alleviate Sensorimotor Deficit in a Rat Model of Huntington Disease

Besusso, Dario ; Schellino, Roberta ; Boido, Marina ; Belloli, Sara ; Parolisi, Roberta ; Conforti, Paola ; Faedo, Andrea ; Cernigoj, Manuel ; Campus, Ilaria and Laporta, Angela , et al. (2020) In Stem Cell Reports 14(5). p.876-891
Abstract

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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
behavioral assessment, brain graft integration, cell replacement therapy, cell transplantation, human embryonic stem cells, Huntington disease, medium spiny neurons, rabies virus-based synaptic tracing, regenerative medicine, striatum
in
Stem Cell Reports
volume
14
issue
5
pages
16 pages
publisher
Cell Press
external identifiers
  • scopus:85084694625
  • pmid:32302555
ISSN
2213-6711
DOI
10.1016/j.stemcr.2020.03.018
language
English
LU publication?
yes
id
3257171a-7aa6-4887-8e64-6a5dc3ec6c03
date added to LUP
2020-06-03 13:18:48
date last changed
2024-06-13 17:07:47
@article{3257171a-7aa6-4887-8e64-6a5dc3ec6c03,
  abstract     = {{<p>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.</p>}},
  author       = {{Besusso, Dario and Schellino, Roberta and Boido, Marina and Belloli, Sara and Parolisi, Roberta and Conforti, Paola and Faedo, Andrea and Cernigoj, Manuel and Campus, Ilaria and Laporta, Angela and Bocchi, Vittoria Dickinson and Murtaj, Valentina and Parmar, Malin and Spaiardi, Paolo and Talpo, Francesca and Maniezzi, Claudia and Toselli, Mauro Giuseppe and Biella, Gerardo and Moresco, Rosa Maria and Vercelli, Alessandro and Buffo, Annalisa and Cattaneo, Elena}},
  issn         = {{2213-6711}},
  keywords     = {{behavioral assessment; brain graft integration; cell replacement therapy; cell transplantation; human embryonic stem cells; Huntington disease; medium spiny neurons; rabies virus-based synaptic tracing; regenerative medicine; striatum}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{876--891}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Stem Cell-Derived Human Striatal Progenitors Innervate Striatal Targets and Alleviate Sensorimotor Deficit in a Rat Model of Huntington Disease}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2020.03.018}},
  doi          = {{10.1016/j.stemcr.2020.03.018}},
  volume       = {{14}},
  year         = {{2020}},
}