Direct and indirect endothelial regulation of neural progenitor cells : a modular approach to understand the neural stem cell niche

Dumont, Courtney Margaret
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Thompson, Deanna M.
Temple, Sally
Dai, Guohao
Plopper, George E.
Hahn, Mariah
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Biomedical engineering
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Each year over 1.5 million Americans incur injuries to their central nervous system (CNS) through traumatic brain or spinal cord injuries. Current treatment options to repair the damaged tissue do not achieve full functional recovery. Adult neural progenitor cells (NPCs) are multi-potent precursor cells capable of repopulating the injury, and thus are being explored for their regenerative capacity. Controlled ex vivo expansion of NPC populations is required to generate sufficient cells for therapeutic transplantation. Understanding the in vivo NPC niche will facilitate the design of better ex vivo expansion methods and may lead to improved viability and repopulation following transplantation. Endothelial cells (ECs) regulate NPC self-renewal and differentiation in vitro through soluble factors, leading to improved ex vivo expansion of neural and oligodendrocyte precursor cells. Previous in vitro EC-NPC models, however, have utilized statically cultured ECs, which are phenotypically different from ECs in vivo, which are exposed to fluid shear stress within the vasculature. Therefore, the goal of this thesis was to develop an in vitro model that utilizes a more physiologically relevant EC phenotype through dynamic stimulation (10 dynes/cm2) from which soluble and insoluble factors can be isolated and used to stimulate NPC proliferation and enrichment of desired NPC phenotypes.
August 2014
School of Engineering
Dept. of Biomedical Engineering
Rensselaer Polytechnic Institute, Troy, NY
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