The individual diagnosed with a neurodegenerative disease suffers with progressive loss of neuronal or glial subtypes. This cell death leads to irreversible loss of structure and function in the affected region of the brain, which can affect the stability of the neuronal circuit. The cause of this degeneration is unknown and currently treatments are limited to ameliorating symptoms. The central nervous system does attempt repair by activating an endogenous pool of neural stem cells, although it is limited, and has not been shown to lead to behavioral recovery, in most instances. An exogenous source of cells could restore the dying population of neurons or glial cells, and delay or eliminate the progression of the disease. Embryonic stem cells are a promising option for exogenous cell replacement therapy, because they can differentiate into developmentally relevant subtypes and integrate into a host neuronal circuit. For embryonic stem cell-based therapies to be effective, we will need to recruit or direct transplanted cells to sites of damage. To investigate the mechanisms for migration after transplant, we studied the role blood vessels play. Previous work from us and others also prompted us to continue or work on the chemokine CXCL12. We demonstrate that transplanted embryonic stem cell-derived neural progenitors associate with, and appear to migrate on the surface of the vasculature in the adult mouse hippocampus. This initial adhesion to vessels is mediated in part, via the integrin α6β1. Our data are also consistent with CXCL12, expressed by the astroglial-vasculature niche, playing an important role in the migration of transplanted neural progenitors upon the vasculature. These results demonstrate that understanding the host brain environment is critical to guide migration and promote incorporation of transplanted cells, which may influence key aspects of invasion and migration in cancer research, as well as downstream signaling of CXCL12.
Lassiter, Chelsea, "Migration of Embryonic Stem Cell-derived Neural Progenitors: Interactions with the Neurovasculature" (2016). Dissertations. 69.
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