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[Report] β-cell–mimetic designer cells provide closed-loop glycemic control

Chronically deregulated blood-glucose concentrations in diabetes mellitus result from a loss of pancreatic insulin-producing β cells (type 1 diabetes, T1D) or from impaired insulin sensitivity of body cells and glucose-stimulated insulin release (type 2 diabetes, T2D). Here, we show that therapeutically applicable β-cell–mimetic designer cells can be established by minimal engineering of human cells. We achieved glucose responsiveness by a synthetic circuit that couples glycolysis-mediated calcium entry to an excitation-transcription system controlling therapeutic transgene expression. Implanted circuit-carrying cells corrected insulin deficiency and self-sufficiently abolished persistent hyperglycemia in T1D mice. Similarly, glucose-inducible glucagon-like peptide 1 transcription improved endogenous glucose-stimulated insulin release and glucose tolerance in T2D mice. These systems may enable a combination of diagnosis and treatment for diabetes mellitus therapy. Authors: Mingqi Xie, Haifeng Ye, Hui Wang, Ghislaine Charpin-El Hamri, Claude Lormeau, Pratik Saxena, Jörg Stelling, Martin Fussenegger

Authors:   Mingqi Xie; Haifeng Ye; Hui Wang; Ghislaine Charpin-El Hamri; Claude Lormeau; Pratik Saxena; Jörg Stelling; Martin Fussenegger
Journal:   Science
Volume:   354
edition:   6317
Year:   2016
Pages:   1296
DOI:   10.1126/science.aaf4006
Publication date:   09-Dec-2016
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