Stem Cell-Derived Human Striatal Progenitors Innervate Striatal Targets and Alleviate Sensorimotor Deficit in a Rat Model of Huntington Disease
(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.
(Less)
- author
- organization
- publishing date
- 2020
- 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
-
- pmid:32302555
- scopus:85084694625
- 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
- 2024-08-21 21:25:13
@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}}, }