ArticleProceedings of the National Academy of Sciences of the United States of America2020
Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05635409 (STEM-PD Trial), which is not on this map. Cited by 38 papers.
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.
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.
STEM-PD Trial: A Multicentre, Single Arm, First in Human, Dose-escalation Trial, Investigating the Safety and Tolerability of Intraputamenal Transplantation of Human Embryonic Stem Cell Derived Dopaminergic Cells for Parkinson's Disease (STEM-PD Product)
Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Construct optimization for AAV-mediated human α-syn overexpression, and validation across research settings: Development of a shared tool for the research community.Journal of Parkinson's disease · 2026Article
- A myeloid trisomy 21-associated gene variant is protective from Alzheimer's disease.Nature neuroscience · 2026Article
- Towards a Biologically Defined Diagnosis: Incorporating Pathophysiological Measures Into Parkinson's Disease Clinical Criteria.Parkinson's disease · 2026Review
- Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.bioRxiv : the preprint server for biology · 2025Article
- Article
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- Long-Term Engraftment of Cryopreserved Human Neurons for In Vivo Disease Modeling in Neurodegenerative Disease.Biology · 2025Article
- Construct, Face, and Predictive Validity of Parkinson's Disease Rodent Models.International journal of molecular sciences · 2024Review
- Past, present, and future of cell replacement therapy for parkinson's disease: a novel emphasis on host immune responses.Cell research · 2024Review
- The hope, hype and obstacles surrounding cell therapy.Journal of cellular and molecular medicine · 2024Review
- A Trisomy 21-linked Hematopoietic Gene Variant in Microglia Confers Resilience in Human iPSC Models of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Host-to-graft propagation of inoculated α-synuclein into transplanted human induced pluripotent stem cell-derived midbrain dopaminergic neurons.Regenerative therapy · 2024Article
- Unravelling the Parkinson's puzzle, from medications and surgery to stem cells and genes: a comprehensive review of current and future management strategies.Experimental brain research · 2024Review
- The AAV-α-Synuclein Model of Parkinson's Disease: An Update.Journal of Parkinson's disease · 2024Review
- Can pluripotent/multipotent stem cells reverse Parkinson's disease progression?Frontiers in neuroscience · 2024Review
- Challenges in the clinical advancement of cell therapies for Parkinson's disease.Nature biomedical engineering · 2023Review
- Challenges involved in cell therapy for Parkinson's disease using human pluripotent stem cells.Frontiers in cell and developmental biology · 2023Review
- Defining the unknowns for cell therapies in Parkinson's disease.Disease models & mechanisms · 2022Article
- Alpha-Synuclein: The Spark That Flames Dopaminergic Neurons, In Vitro and In Vivo Evidence.International journal of molecular sciences · 2022Article
- Association of ATG5 gene polymorphism with Parkinson's disease in a Han Chinese population.Acta neurologica Belgica · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better recapitulates the main disease features, obtained by coinjection of preformed human α-synuclein (α-syn) fibrils and adeno-associated virus (AAV) expressing human wild-type α-syn unilaterally into the rat substantia nigra (SN). This model gives rise to DA neuron dysfunction and progressive loss of DA neurons from the SN and terminals in the striatum, accompanied by extensive α-syn pathology and a prominent inflammatory response, making it an interesting and relevant model in which to examine long-term function and integrity of transplanted neurons in a PD-like brain. We transplanted DA neurons derived from human embryonic stem cells (hESCs) into the striatum and assessed their survival, growth, and function over 6 to 18 wk. We show that the transplanted cells, even in the presence of ongoing pathology, are capable of innervating the DA-depleted striatum. However, on closer examination of the grafts, we found evidence of α-syn pathology in the form of inclusions of phosphorylated α-syn in a small fraction of the grafted DA neurons, indicating host-to-graft transfer of α-syn pathology, a phenomenon that has previously been observed in PD patients receiving fetal tissue grafts but has not been possible to demonstrate and study in toxin-based animal models.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.