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Science. 2016 Dec 9;354(6317):1296-1301.

β-cell-mimetic designer cells provide closed-loop glycemic control.

Author information

1
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
2
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, 200241 Shanghai, China.
3
Institut Universitaire de Technologie, IUT, Département Génie Biologique, F-69622 Villeurbanne Cedex, France.
4
SIB-Swiss Institute of Bioinformatics, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
5
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland. fussenegger@bsse.ethz.ch joerg.stelling@bsse.ethz.ch.
6
University of Basel, Faculty of Science, Mattenstrasse 26, CH-4058 Basel, Switzerland.

Abstract

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.

Comment in

PMID:
27940875
DOI:
10.1126/science.aaf4006
[Indexed for MEDLINE]

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