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.
Original language | English (US) |
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Pages (from-to) | 3456-3472 |
Number of pages | 17 |
Journal | Brain |
Volume | 142 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2019 |
Keywords
- Co-stimulation blockade
- Glial-restricted progenitors
- Immunological tolerance
- Myelination
- Transplantation
ASJC Scopus subject areas
- Clinical Neurology