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Role of Matrix Microenviroment on Neural Stem Cell Phenotype and Differentiation under Healthy and Inflammatory Conditions

Farrell, Kurt W.
http://rave.ohiolink.edu/etdc/view?acc_num=csu1462009482

Abstract Details

2016, Doctor of Engineering, Cleveland State University, Washkewicz College of Engineering.
Localized host inflammatory microenvironment resulting from several neuropathologies (e.g., trauma, amyotrophic lateral sclerosis (ALS), glioblastomas) leads to progressive degeneration of neuronal tissue and destruction of axonal tracts in the adult central nervous system (CNS). Failure to reinstate healthy cells and axonal connections under these conditions can severely compromise locomotion and cognitive function, resulting in muscle atrophy, paralysis and even death. Annually, thousands of people are diagnosed with various neuropathologies and a majority of them succumb to these conditions soon after. The adult CNS has a limited ability for self-repair, which necessitates repair strategies focused on ameliorating secondary cellular degeneration, promoting endogenous repair mechanisms, and exogenous cell replacement therapy. Currently, pharmacological and surgical treatments options are limited in their outcomes for these types of ailments. Neural stem cells (NSCs) isolated from the embryonic and adult striatum have the capacity to divide and differentiate into various neuronal and glial lineages, thus demonstrating their utility in regenerating lost neuronal populations. To further investigate their clinical potential, in this work, we first developed and tested the utility of uncrosslinked 3D biological hydrogels (compressive strength < 600 Pa) for their ability to promote murine NSC survival, differentiation into desired lineages and neurite outgrowth, in the presence (or absence) of exogenous cues such as retinoic acid. In the second step, the influence of an activated murine microglia in regulating the phenotype and genotype of murine NSCs within a localized 3D coculture microenvironment was investigated, and the key cytokines and chemokines which regulate NSC survival, differentiation and neurite outgrowth were identified. Finally, in the third step, the effects of paracrine-signaling between adult human NSCs and human pediatric glioblastoma cells within a coculture microenvironment, in regulating their survival, proliferation, migration, differentiation and axonal outgrowth were investigated. Results from this work provide insights into neural stem cell interactions with 3D biological matrices, inflammatory microenvironment, and glioblastoma cells, which could lead to development of strategies for CNS repair and regeneration utilizing NSC transplantation techniques.
Chandra Kothapalli, Ph.D. (Committee Chair)
Nolan Holland, Ph.D. (Committee Member)
Xue-Long Sun, Ph.D. (Committee Member)
Joanne Belovich, Ph.D. (Committee Member)
Moo-Yeal Lee, Ph.D. (Committee Member)
207 p.
Biomedical Engineering; Medicine; Neurosciences
biomedical engineering; tissue engineering; regenerative medicine; neural stem cells; microglia; glioblastoma; ECM hydrogels; rheology; differentiation; stem cell biology; cytokines and chemokines; neurological disorders

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Citations

  • Farrell, K. W. (2016). Role of Matrix Microenviroment on Neural Stem Cell Phenotype and Differentiation under Healthy and Inflammatory Conditions [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1462009482

    APA Style (7th edition)

  • Farrell, Kurt. Role of Matrix Microenviroment on Neural Stem Cell Phenotype and Differentiation under Healthy and Inflammatory Conditions. 2016. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1462009482.

    MLA Style (8th edition)

  • Farrell, Kurt. "Role of Matrix Microenviroment on Neural Stem Cell Phenotype and Differentiation under Healthy and Inflammatory Conditions." Doctoral dissertation, Cleveland State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1462009482

    Chicago Manual of Style (17th edition)

csu1462009482
421
© 2016, some rights reserved.Creative Commons License Role of Matrix Microenviroment on Neural Stem Cell Phenotype and Differentiation under Healthy and Inflammatory Conditions by Kurt W. Farrell is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Cleveland State University and OhioLINK.