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    Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration

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    Author
    Malysz-Cymborska, I.
    Golubczyk, D.
    Kalkowski, L.
    Kwiatkowska, J.
    Zawadzki, M.
    Głodek, J.
    Holak, P.
    Sanford, J.
    Milewska, K.
    Adamiak, Z.
    Walczak, P.
    Janowski, M.
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    Date
    2021-03-22
    Journal
    Scientific Reports
    Publisher
    Nature Research
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1038/s41598-021-85820-3
    Abstract
    Stem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Canine GRP transplantation in dogs resulted in rather poor retention in the brain, so MSCs were used in subsequent experiments. To evaluate the safety of MSC intraarterial transplantation, naïve pigs (n = 3) were used as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. The procedure in pigs has proven to be safe and histopathology has demonstrated the successful and predictable placement of transplanted porcine MSCs. Transplantation of canine MSCs in DM dogs resulted in their accumulation in the brain. Interventional and follow-up MRI proved the procedure was feasible and safe. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases. Copyright 2021, The Author(s).
    Keyword
    intra-arterial transplantation
    Mesenchymal Stem Cell Transplantation--methods
    Models, Animal
    Neurodegenerative Diseases
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15173
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-021-85820-3
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