A novel approach for pancreatic beta-cell differentiation in vitro and in vivo

Funding Type: 
SEED Grant
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 
Our bodies are made of about 2 billions of different cell types that have their own functions. Diseases like diabetes are largely caused by a breakdown in cell function or by cell death. The major issue of diabetes is an inability to control the level of glucose (sugar) in the blood. Blood glucose levels are normally controlled by insulin produced by islet cells of pancreas. In people with Type I diabetes islet cells are being destroyed by autoimmune system, which is mainly occurred in children. A lifetime of diabetes results in severe and debilitating consequences including kidney failure, adult blindness, nerve damage and cardiovascular disease (leading to limb amputations, heart attack and stroke). The majority of current constructive techniques rely on supply of donor tissues for replacement; however, the major hurdle is finding enough number of human islets to be transplanted into all the people who is waiting on the list for this treatment. The supply of islets donated from cadaver will never be balanced with demand. There is currently no available cure for diabetes that would prevent the occurrence of these consequences. This reality has driven researchers and clinicians to find alternate strategies to cure diabetes. An ideal pancreas, which reproduces the physiological response of the normal pancreas to the glucose changing, would drastically reduces the occurrence of secondary illness and improve the quality of live of diabetic people. Embryonic stem cells (ESC) can make all cell types existing in human body, however at the moment they can not be used for clinical application because the risk of tumor formation and the lack of knowledge for efficient differentiation in insulin-producing cells. We propose to create a novel human cellular system that will address these unmet need, especially for cell therapy. Our goal is to prune all bad characteristics of ESC by selecting a new population of cells from ESC, which can not only maintain to grow indefinitely but also produce enough number of clinical grade cells to make up the destroyed insulin-secreting cells. Our new cells will be called pruned-ESC. In order to demonstrate that insulin producing cells from our pruned-ESC be safely used, we will combine gene and cell therapies for curing Type I diabetes. We will insert an active master gene into pruned-ESC, which is crucial for normal development of pancreas, particularly for insulin-producing cells. Pruned-ESC with a master gene will be given to Type I diabetic mice to evaluate the feasibility of our system for clinical application. We believe that our combined gene and cell technology along with pruned-ESC will allow us to investigate that reasons of Type I diabetes and offer an evidence that is Type I diabetes can be curable in the near future.
Statement of Benefit to California: 
Diabetes mellitus (DM) is estimated to affect approximately 18.2 million people in the US alone, and more than 150 million people worldwide. California’s ethnically diverse population is disproportionately affected by diabetes. The overall prevalence of diabetes among California adults is increasing. A study by UCLA Center for Health Policy Research, comparing the years 2001 and 2003, showed that in 2003 nearly 1.7 million California adults age 18 and over (6.6%) has been diagnostic with diabetes in 2003, up from 1.5 million (6.2%) in 2001. By the year 2020, the prevalence of diabetes in California is expected to exceed four million people. Without normal glucose homeostasis over the long term, complications involving the eyes, kidneys, nerves and cardiovascular system are common, which reduce quality of life and significantly increase morbidity, mortality, and cost. For this reason new therapeutic solutions for diabetes should be a priority for California. Stem cell research is among the hottest fields in today’s medical research because these cells have the potential to replace cells that are dysfunctional or lost. The use of stem cells for curing disease and ending disabilities may change the medical treatment in this century. However, there are some major roadblocks that need to be resolved before these cells are implemented in ordinary medical care. Reliable methods for isolation and expansion of stem cells need to be established, efficient differentiation protocols need to be developed, and stem cell plasticity causing tumorigenicity needs to be controlled. This proposal aims to address all of these roadblocks. We will use a novel approach to select a new stem cell population from human embryonic stem cells, which retain differentiation capability but lose propensity for teratoma formation. Our overall goal is to evaluate the potential use of this novel stem cell system for the treatment of a devastating, yet incurable, disease, diabetes mellitus. If we succeed this project our developed system may become the basic of new treatment solutions for diabetes, giving the California a clear competitive advantage over other states in area of stem cell research.

© 2013 California Institute for Regenerative Medicine