Student Theses and Dissertations

Date of Award

2009

Document Type

Thesis

RU Laboratory

Strickland Laboratory

Keywords

peripheral neuropathies, adipose derived stem cells, Tumor Necrosis Factor (TNF)

Abstract

Peripheral neuropathies are a significant cause of morbidity and mortality, with a population prevalence of 2,400 per 100,000 (2.4%) that increases in the elderly to 8,000 per 100,000 (8%)(C. N. Martyn and R. A. Hughes, 1997). The variations in symptom distribution and etiologic attribution have resulted in the classification of over 100 types of peripheral neuropathy with specific patterns of development and prognoses. In the first study, we use a mouse model of hereditary peripheral neuropathy that results in hind-limb paralysis to investigate the therapeutic efficacy of adult, adipose derived stem cells (ADSC). The paralyzed mice that received ADSC transplantation demonstrated significantly improved motor function, likely due to stromal support provided by ADSCs. The ultrastructure of the nerve was not significantly improved, indicating that the threshold of functional motor improvement can be met through alternative means. In the second study, we developed a process to identify highly-connected genes in a model of peripheral nerve development using entropy maximized network analysis of gene microarrays. We found that Tumor Necrosis Factor (TNF) mediates axonal-Schwann cell communication, and that disruption of TNF signaling results in sensory and tissue dysfunction. These findings indicate that the threshold of wild-type physiological function in peripheral nerve development can be addressed by disrupting or strengthening specific signaling processes without significant changes to tissue structure.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/405

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