Histological evaluation of the propagation of α-synuclein into grafted human induced pluripotent stem cell-derived neurons Article Swipe

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Kaneyasu Nishimura , Serina Gima , Takashi Ohgita , Hiroyuki Saito , Kazuyuki Takata ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1254/jpssuppl.97.0_2-b-p-050

Clinical trials of cell transplantation therapy using fetal mesencephalic tissue provided a proof-of-concept for regenerative therapy for the patients with Parkinson's disease. Postmortem studies of the patients who received fetal grafts revealed that α-synuclein (α-syn)+ Lewy body-like inclusions were emerged in long-term transplantation and may reduce the clinical outcomes even the grafts were well survived in the recipients. Various studies were conducted to reveal that the host derived α-syn are transferred to the grafted neurons to assess the exsert of α-syn+ inclusions in the grafts. However, these studies remain the possibility to detect the intrinsic expression of α-syn in the grafted neurons. Here, we demonstrated that the human α-syn preformed fibrils inoculated into the cerebral cortex were transferred to SNCA-/- human induced pluripotent stem cell-derived midbrain dopaminergic (mDA) neurons grafted into the striatum of rats. Because grafted SNCA-/- hiPSC-derived mDA neurons lack the intrinsic expression of α-syn protein, the human α-syn-immunoreactivity found in the grafted cells should be derived from the host brain. Our results clearly showed that host-to-graft propagation of α-syn was occurred, and this work contributes to understand the molecular mechanisms to form the α-syn inclusions in the grafted mDA neurons.

Related Topics

Hematopoietic Stem Cell Transplantation

Concepts

Induced pluripotent stem cell Transplantation Striatum Parkinson's disease Biology Substantia nigra Dopaminergic Pathology Neuroscience Human brain Cell biology Embryonic stem cell Dopamine Medicine Disease Internal medicine Biochemistry Gene

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Type: article
Language: en
Landing Page: https://doi.org/10.1254/jpssuppl.97.0_2-b-p-050
PDF: https://www.jstage.jst.go.jp/article/jpssuppl/97/0/97_2-B-P-050/_pdf
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DOI: https://doi.org/10.1254/jpssuppl.97.0_2-b-p-050

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Title: Histological evaluation of the propagation of α-synuclein into grafted human induced pluripotent stem cell-derived neurons

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Language: en

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Publication year: 2023

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Publication date: 2023-01-01

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Authors: Kaneyasu Nishimura, Serina Gima, Takashi Ohgita, Hiroyuki Saito, Kazuyuki Takata

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Landing page: https://doi.org/10.1254/jpssuppl.97.0_2-b-p-050

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Concepts: Induced pluripotent stem cell, Transplantation, Striatum, Parkinson's disease, Biology, Substantia nigra, Dopaminergic, Pathology, Neuroscience, Human brain, Cell biology, Embryonic stem cell, Dopamine, Medicine, Disease, Internal medicine, Biochemistry, Gene

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abstract_inverted_index.assess	76
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