ArticleStem cell research & therapy2023
hESC-derived striatal progenitors grafted into a Huntington's disease rat model support long-term functional motor recovery by differentiating, self-organizing and connecting into the lesioned striatum.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Brain injury reactivates a developmental program driving genesis and integration of transient LGE-class interneurons.Stem cell reports · 2026Article
- Modeling striatal development and disease with human pluripotent stem cells.Inflammation and regeneration · 2026Review
- Environmental enrichment as a mitochondria-targeting systems strategy across neurodegenerative diseases and retinal dystrophies.Frontiers in neuroscience · 2026Review
- The Evolving Landscape of Stem Cell Therapies for Huntington's Disease.Molecular diagnosis & therapy · 2026Review
- Gelatin methacryloyl hydrogel as a potential scaffold for cell transplantation for Huntington's disease.Brain communications · 2026Article
- Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies.Neuron · 2025Review
- Advances in gene and cellular therapeutic approaches for Huntington's disease.Protein & cell · 2025Review
- Reprogrammed human lateral ganglionic eminence precursors generate striatal neurons and restore motor function in a rat model of Huntington's disease.Stem cell research & therapy · 2024Article
- Transplanted human neural stem cells rescue phenotypes in zQ175 Huntington's disease mice and innervate the striatum.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuntington's disease (HD) is a motor and cognitive neurodegenerative disorder due to prominent loss of striatal medium spiny neurons (MSNs). Cell replacement using human embryonic stem cells (hESCs) derivatives may offer new therapeutic opportunities to replace degenerated neurons and repair damaged circuits.
methodsWith the aim to develop effective cell replacement for HD, we assessed the long-term therapeutic value of hESC-derived striatal progenitors by grafting the cells into the striatum of a preclinical model of HD [i.e., adult immunodeficient rats in which the striatum was lesioned by monolateral injection of quinolinic acid (QA)]. We examined the survival, maturation, self-organization and integration of the graft as well as its impact on lesion-dependent motor alterations up to 6 months post-graft. Moreover, we tested whether exposing a cohort of QA-lesioned animals to environmental enrichment (EE) could improve graft integration and function.
resultsHuman striatal progenitors survived up to 6 months after transplantation and showed morphological and neurochemical features typical of human MSNs. Donor-derived interneurons were also detected. Grafts wired in both local and long-range striatal circuits, formed domains suggestive of distinct ganglionic eminence territories and displayed emerging striosome features. Moreover, over time grafts improved complex motor performances affected by QA. EE selectively increased cell differentiation into MSN phenotype and promoted host-to-graft connectivity. However, when combined to the graft, the EE paradigm used in this study was insufficient to produce an additive effect on task execution.
conclusionsThe data support the long-term therapeutic potential of ESC-derived human striatal progenitor grafts for the replacement of degenerated striatal neurons in HD and suggest that EE can effectively accelerate the maturation and promote the integration of human striatal cells.
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