Immunogenic properties of neuralized embryonic stem cells in a model of allogenic intracranial transplantation
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Intracranial stem cell transplantation has may restore central nervous system (CNS) function and compensate for neural cell loss. However, immunological rejection of stem cells can limit the effectiveness of such therapy. Neuralized embryonic stem cells (nESCs) were grafted into the striatum of murine hosts and monitored from 3 days to 6 weeks post-transplantation. Allogeneic nESCs were rapidly rejected brain grafts over the course of 7 days, while syngeneic grafts persisted for greater than 14 days. Our results indicate that rejection of nESCs occurs within the CNS, and demonstrates that intraparenchymal antigens can recruit a systemic immune response; the adaptive immune system is strongly implicated in the destruction of graft tissue. We also describe a novel NSC culture system with the potential for intracranial transplantation, derived from ES cells, that maintains and expands a population of neural stem cells similar to those in the developing and adult brain. FLOW cytometry, qRT-PCR, and immunocytochemistry were used to examine the unique structures formed by embryonic stem cells that exhibit key properties of a developing neural stem cell niche. We believe this system to have promising applications in stem cell transplantation, emphasizing the importance of understanding graft rejection in the brain in order to effectively introduce and preserve this complex microenvironment in intracranial transplantation therapy.
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