Biomarkers for Diabetes using Stem Cell-derived Beta Cells
Contact PI: Douglas Melton, PhD, Harvard University (UC4 DK104159)
Start Date: September 23, 2014
End Date: August 31, 2018
Abstract
The diagnosis of Type 1 diabetes (T1D) is currently limited by methods that detect the disease at relatively late stages, when blood glucose levels rise and autoimmune attack is well underway. By this stage, given the treatments presently available (insulin injection), the β cell loss is de facto, irreversible. Biomarkers for early detection of B cell stress, before this late stage, would improve diagnosis and open up new windows to monitor and possibly treat the disease. We will produce functionally mature, “never-before-stressed”, β cells from human pluripotent cells and use these cells to identify biomarkers for the earliest stages of β cell stress by providing various stress conditions ex vivo. In addition, we can use pluripotent cells from T1D and control patients to investigate differences in their β cell responses to stress. In other words, we can ask: are β cells in T1D patients especially sensitive to stress or in other ways defective before an immune attack? Successful identification of early β cell-specific biomarkers for stress will enable earlier detection and diagnosis, better tracking f progress from asymptomatic to clinical presentation, and a more mechanistic understanding of the earliest stages and possibly initiating events of human T1D.
Publications
- IAPP Marks Mono-hormonal Stem-cell Derived β Cells that Maintain Stable Insulin Production in vitro and in vivo
- Purification of Live Stem-Cell-Derived Islet Lineage Intermediates
- Glucose Response by Stem Cell-Derived β Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis
- Live Cell Monitoring and Enrichment of Stem Cell-Derived β Cells Using Intracellular Zinc Content as a Population Marker
- Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development
- Charting cellular identity during human in vitro β-cell differentiation
- A Peninsular Structure Coordinates Asynchronous Differentiation with Morphogenesis to Generate Pancreatic Islets
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