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The Role Of C-Kit Receptor Tyrosine Kinase In Beta-Cell Proliferation, Function And Survival, Zhi Chao Feng

Electronic Thesis and Dissertation Repository

c-Kit, a receptor tyrosine kinase, interacts with Stem Cell Factor (SCF), mediating cell differentiation, function, and survival. c-Kit is critical for the development and maintenance of beta-cell function in both rodents and humans. The mutation of c-Kit at W locus (c-Kit^Wv/+) in mice results in an early onset of diabetes. However, the underlying mechanisms by which c-Kit deficiency leads to beta-cell failure are unknown. Therefore, studying SCF/c-Kit downstream signaling pathways is essential to understanding the precise mechanism by which c-Kit regulates beta-cell survival and function in vivo.

We identified that dysregulated Akt/Glycogen synthase kinase 3β (Gsk3β)/cyclin …

Islet Regenerative Properties Of Ex Vivo Expanded Hematopoietic Progenitor Cells, Ayesh K. Seneviratne

Electronic Thesis and Dissertation Repository

Human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH^hi), can stimulate endogenous islet regeneration after transplantation into mice with steptozotocin (STZ)-induced diabetes. However, UCB ALDH^hi cell are extremely rare, and expansion will be required to develop cell-mediated strategies to treat patients with diabetes. To increase the number of progenitor cells available for clinical application, we expanded ALDH^hi UCB cells under clinically applicable, serum-free hematopoietic-restricted conditions. 6 day expansion resulted in a 15-fold increase in total cell number, and a 3-fold increase in the number of HPC retaining high ALDH (ALDH^hi HPC) …

The Role Of Integrins In Support Of Pancreatic Function, Survival And Maturation, Matthew Riopel

Electronic Thesis and Dissertation Repository

The pancreas is a glandular organ composed of endocrine and exocrine compartments. Integrins are cell adhesion molecules that connect cells to the extracellular matrix (ECM). Integrins modulate a variety of cellular effects, yet their mechanism of action in the developed pancreas is not well understood. Fibrin is a provisional ECM protein that contains ligands for integrin receptors. Fibrin is capable of supporting islet health, but it is unclear how fibrin exerts its effects. The objective of this thesis is to understand the role of integrin receptors on in vivo pancreatic cell function, survival, and proliferation. In addition, this thesis investigates …