4.7 Review

Postmortem Studies of Fetal Grafts in Parkinson's Disease: What Lessons Have We Learned?

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.666675

Keywords

Parkinson's disease; grafts; Lewy pathology; postmortem studies; transplantation

Funding

  1. National Natural Science Foundation [81430025]
  2. National Natural Science foundation of China [NSFC: 31800898]
  3. Swedish Research Council [K2015-61X-22297-03-4]
  4. EU Joint Program-Neurodegenerative Disease Research (aSynProtec and REfreAME), EU H2020-MSCA-ITN-2016 (Syndegen)
  5. Basal Ganglia Disorders Linnaeus Consortium-Excellence in Parkinson and Huntington Research
  6. Strong Research Environment MultiPark (Multidisciplinary Research on Parkinson's disease)
  7. Swedish Parkinson Foundation (Parkinsonfonden)
  8. Torsten Soderbergs Foundation
  9. Olle Engkvist Byggmastere Foundation

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The review focused on fetal dopaminergic neuron transplantation therapies for Parkinson's disease, highlighting the clinical outcomes and neuroanatomy of grafted cases, as well as postmortem studies including cell survival, reinnervation, and pathology development. The discussion aimed at understanding the link between function and structure of the grafts to identify factors contributing to a functional graft for future transplantation trials.
Neural transplantation is a potential therapeutic method for Parkinson's disease (PD). Fetal dopaminergic (DA) neurons have been important transplantation cell sources in the history of replacement therapy for PD. Several decades of preclinical animal experiments and clinical trials using fetal DA neuron transplantation in PD therapy have shown not only promising results but also problems. In order to reveal possible factors influencing the clinical outcomes, we reviewed fetal DA neuron transplantation therapies from 1970s to present, with a special focus on postmortem studies. Firstly, we gave a general description of the clinical outcomes and neuroanatomy of grafted cases; secondly, we summarized the main available postmortem studies, including the cell survival, reinnervation, and pathology development. In the end, we further discussed the link between function and structure of the grafts, seeking for the possible factors contributing to a functional graft. With our review, we hope to provide references for future transplantation trials from a histological point of view.

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