Masters Thesis

Effect of human progenitor cells on an animal model of type 1 diabetes

This project focuses on a novel progenitor cell therapy for type 1 diabetes, a chronic illness that is categorized by pancreatic beta cell death. The current advancements in diabetes research has brought attention to innovative cellular applications that can help increase insulin production. Here, human progenitor cells were used to mimic and replace beta cells in a diabetic rat model induced by a one-time intraperitoneal injection of streptozotocin that selectively damages beta cells. The effects of inducing diabetes were examined by testing blood glucose levels daily using Accu-Chek glucometers. After establishing diabetes in the rats (400mg/dL glucose), preparation for transplantation began by immunosuppressing the diabetic rat using Alzet pumps that chronically administers cyclosporine over the course of 23 days. During this time, blood glucose and weight were monitored to ensure the rat's viability for successful transplant surgery and post-surgery outcomes. Next, live human progenitor cells, live differentiated pancreatic progenitor cells and dead human progenitor cells (control) were injected into different regions of the diabetic rat: the circulatory system, peritoneal cavity, pancreas, and kidney capsule. The last two treatments require an additional surgery of exposing either the pancreas or kidney capsule in order to transplant the human progenitor cells. Finally, immunohistochemistry of the rat's organs showed the presence of surviving human progenitor cells in the kidney capsule 37 days post-transplantation. One day after cell treatment, pancreatic progenitor cell treatment group via kidney capsule had significant decrease in blood glucose levels (p0.005) compared to dead progenitor cells injected into the kidney capsule blood glucose levels. This experiment aimed to alleviate pancreatic beta cell death and possibly be one step closer to curing type 1 diabetes.

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