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(2009)ThesisRegenerative biology seeks to understand the molecular mechanisms that differentiate several animals with the ability to regenerate tissues. An approach to evaluate these mechanisms is via a comparative analysis of regeneration-competent versus regeneration-deficient tissues. This thesis analyses the regenerative capacity in the axolotl blastema during the dedifferentiation phase. Currently, there is an equivocal understanding of the molecular factors expressed during the regenerative process and further analysis is warranted. Comprehensive profiles of the proteins expressed during this process are presented. Nerve derived factors such as neuregulin-1 and neurotrophin-3 were identified in the axolotl blastema during the time of dedifferentiation. Additionally, this study investigated if there are any correlation between the nerve determinants, such as neurotrophins, from the regenerating blastema and neurogenesis that occurs throughout the lifespan of mammals in the olfactory system. This was achieved by comparing the expression proteomes of the regeneration-competent axolotl and olfactory ensheathing cells. Collectively, the study proposes that there is an influence by neurotrophins on neurogenesis in the olfactory system that are comparable to the dynamic nerve signaling networks that occur in the axolotls regenerating limb. It provides a window into the complex signaling pathways during the two processes that can be clinically translated to further develop better therapeutic strategies that involve peripheral nervous tissue of the spinal cord. The current clinical outcomes usually result in limited functional restoration. One of the most promising techniques is to induce a regenerative capacity in the affected tissues using a tissue engineering strategy. The combination of factors identified may serve as candidates to augment in vivo peripheral nerve microenvironments and to achieve a regenerative capacity in human tissues. These neurotrophins should be considered for regenerative medicine applications to induce regenerative competence in human peripheral nerve tissues.
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