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DOI10.1126/science.aau7187
Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice
Krawczyk K.; Xue S.; Buchmann P.; Charpin-El-Hamri G.; Saxena P.; Hussherr M.-D.; Shao J.; Ye H.; Xie M.; Fussenegger M.
发表日期2020
ISSN0036-8075
起始页码993
结束页码1001
卷号368期号:6494
英文摘要Sophisticated devices for remote-controlled medical interventions require an electrogenetic interface that uses digital electronic input to directly program cellular behavior. We present a cofactor-free bioelectronic interface that directly links wireless-powered electrical stimulation of human cells to either synthetic promoter-driven transgene expression or rapid secretion of constitutively expressed protein therapeutics from vesicular stores. Electrogenetic control was achieved by coupling ectopic expression of the L-type voltage-gated channel CaV1.2 and the inwardly rectifying potassium channel Kir2.1 to the desired output through endogenous calcium signaling. Focusing on type 1 diabetes, we engineered electrosensitive human β cells (Electroβ cells). Wireless electrical stimulation of Electroβ cells inside a custom-built bioelectronic device provided real-time control of vesicular insulin release; insulin levels peaked within 10 minutes. When subcutaneously implanted, this electrotriggered vesicular release system restored normoglycemia in type 1 diabetic mice. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词celldiabeteshormonepeptidereal timerodentMuscalcium channel L typeinwardly rectifying potassium channelinwardly rectifying potassium channel subunit Kir2.1L-type calcium channel alpha(1C)animalcalcium signalingcell engineeringdeviceselectrostimulationexperimental diabetes mellitusgenetic transcriptiongeneticsHEK293 cell linehumaninsulin dependent diabetes mellitusinsulin releasemalemetabolismmousepancreas islet beta cellprostheses and orthosestransgenewireless communicationAnimalsBionicsCalcium Channels, L-TypeCalcium SignalingCell EngineeringDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Electric StimulationHEK293 CellsHumansInsulin SecretionInsulin-Secreting CellsMaleMicePotassium Channels, Inwardly RectifyingProstheses and ImplantsTranscription, GeneticTransgenesWireless Technology
语种英语
来源机构Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/133471
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Krawczyk K.,Xue S.,Buchmann P.,et al. Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice[J]. Science,2020,368(6494).
APA Krawczyk K..,Xue S..,Buchmann P..,Charpin-El-Hamri G..,Saxena P..,...&Fussenegger M..(2020).Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice.,368(6494).
MLA Krawczyk K.,et al."Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice".368.6494(2020).
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