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Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts
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Li, Shen, Oh, Byoung Chol, Chu, Chengyan, Arnold, Antje, Jablonska, Anna, Furtmüller, Georg J., Qin, Hua-Min, Boltze, Johannes, Magnus, Tim, Ludewig, Peter, Janowski, Mirosław, Brandacher, Gerald and Walczak, Piotr (2019) Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts. Brain, 142 (11). pp. 3456-3472. doi:10.1093/brain/awz275
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WRAP-induction-immunological-tolerance-myelinogenic-glial-restricted-Boltze-2019.pdf - Accepted Version - Requires a PDF viewer. Download (7Mb) | Preview |
Official URL: https://doi.org/10.1093/brain/awz275
Abstract
The immunological barrier currently precludes the clinical utilization of allogeneic stem cells. Although glial-restricted progenitors have become attractive candidates to treat a wide variety of neurological diseases, their survival in immunocompetent recipients is limited. In this study, we adopted a short-term, systemically applicable co-stimulation blockade-based strategy using CTLA4-Ig and anti-CD154 antibodies to modulate T-cell activation in the context of allogeneic glial-restricted progenitor transplantation. We found that co-stimulation blockade successfully prevented rejection of allogeneic glial-restricted progenitors from immunocompetent mouse brains. The long-term engrafted glial-restricted progenitors myelinated dysmyelinated adult mouse brains within one month. Furthermore, we identified a set of plasma miRNAs whose levels specifically correlated to the dynamic changes of immunoreactivity and as such could serve as biomarkers for graft rejection or tolerance. We put forward a successful strategy to induce alloantigen-specific hyporesponsiveness towards stem cells in the CNS, which will foster effective therapeutic application of allogeneic stem cells.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Myelination, Stem cells, Immunological tolerance, Homografts | |||||||||||||||
| Journal or Publication Title: | Brain | |||||||||||||||
| Publisher: | Oxford University Press | |||||||||||||||
| ISSN: | 0006-8950 | |||||||||||||||
| Official Date: | November 2019 | |||||||||||||||
| Dates: |
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| Volume: | 142 | |||||||||||||||
| Number: | 11 | |||||||||||||||
| Page Range: | pp. 3456-3472 | |||||||||||||||
| DOI: | 10.1093/brain/awz275 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Publisher Statement: | This is a pre-copyedited, author-produced version of an article accepted for publication in Brain following peer review. The version of record, Induction of immunological tolerance to myelinogenic glial-restricted progenitor allografts, Brain, Volume 142, Issue 11, November 2019, Pages 3456–3472 is available online at: https://doi.org/10.1093/brain/awz275 | |||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||
| RIOXX Funder/Project Grant: |
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