Type I diabetes (TID) patients suffer from insufficient or lack of insulin to regulate blood glucose levels. Due to loss of pancreatic beta-cells, the only treatment for TID patient is transplantation of donor islets. With the improved transplantation technique, it still requires 2-4 donor pancreas for each successful transplantation. The shortage of donor islets and inefficiency of beta-cell regeneration presented an urgent need for alternative sources of beta-cells. Embryonic stem (ES) cell-derived insulin producing cells are regarded as a possible means to overcome these limitations. However, difficulties in controlling the fate of ES cell differentiation have presented significant challenge for using ES cells to treat type I diabetes. Current protocols of ES cell differentiation to beta-cells rely on trying different combinations of medium factors. A lack of monitoring system has made the effort to improve the beta-cell proliferation protocol a blind search. In this grant proposal, we intend to design a monitoring system to monitor the differentiation process. This monitoring system is based on the physiological development of the pancreas. During pancreas development, several distinct stage with different cell markers have been identified to be critical. Using these markers as a monitoring guide will aid in our effort of improving beta-cell differentiation protocol. In this study, we propose to design fluorescent reporter markers to monitor the appearance and disappearance of these markers. The system designed here will be useful tools for future studies targeted at improving the current beta-cell differentiation protocol. A efficient and reliable beta-cell differentiation protocol is the critical step toward using ES cell based therapy for the treatment of type I diabtetes.
The proposed study is an important step towards establishing a reliable, robust differentiation system for beta-cells. The percentage of population who has diabetes in California is among the top in the 50 states. Therefore, a treatment targeted at diabetes will be of significant benefit to the California citizens. For type I diabetes for whom transplantation is the only reliable treatment, an alternative treatment is urgently needed and is of significant benefit to the Californians.