Effects of culture dimensionality and hypoxia on human neural stem cells
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Date
2016-01-01
Type of Work
Department
Chemical, Biochemical & Environmental Engineering
Program
Engineering, Chemical and Biochemical
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This item may be protected under Title 17 of the U.S. Copyright Law. It is made available by UMBC for non-commercial research and education. For permission to publish or reproduce, please see http://aok.lib.umbc.edu/specoll/repro.php or contact Special Collections at speccoll(at)umbc.edu
Distribution Rights granted to UMBC by the author.
Distribution Rights granted to UMBC by the author.
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Abstract
Neurodegenerative diseases result in the loss of brain cells, causing difficulties in movement and mental functioning of patients. Currently, there is no effective therapy with the capability of modifying disease symptoms in the long-term. Transplantation of human neural stem cells (NSCs) is a novel treatment modality with the ability to regenerate the damaged neural tissue. NSCs possess two unique characteristics: the ability to renew themselves through cell division (self-renewal), and the capability to differentiate into major brain cell types (neurons, astrocytes, and oligodendrocytes). Therefore, NSCs present a renewable source of cells with tissue-specific regenerative capacity and, hence, are promising therapeutic candidates. However, limited availability of stem cells, lack of standardized protocols for cell preparation as well as low survival of NSCs after transplantation are among important challenges that restrict the translational potential of NSC-mediated therapy. We hypothesize that the discrepancy between in vitro culture methods and the native brain microenvironment may be an underlying reason for this restricted translational potential. For enhanced therapeutic efficacy, the in vitro culture methods utilized for propagation of the cells need to be improved. Culture dimensionality, reduced oxygen concentration (hypoxia), growth factors, and interactions between cells and the extracellular matrix are among important culture parameters that differ between in vitro and in vivo situations. In this work, we present quantitative data supporting that these culture parameters can individually and synergistically regulate NSC survival, proliferation, differentiation, and cellular output. This work is a major step towards understanding key factors that regulate NSC fate and provides a foundation for improved strategies to more efficiently harness the regenerative potential of human NSCs.