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Bioengineered Pancreas–Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia
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- Shafagh, Reza Zandi (author)
- Karolinska Institutet,KTH,Mikro- och nanosystemteknik,Department of Physiology and Pharmacology Karolinska Institutet Stockholm 17711 Sweden
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- Youhanna, Sonia (author)
- Department of Physiology and Pharmacology Karolinska Institutet Stockholm 17711 Sweden
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- Keulen, Jibbe (author)
- KTH,Mikro- och nanosystemteknik,Department of Physiology and Pharmacology Karolinska Institutet Stockholm 17711 Sweden; Dr Margarete Fischer‐Bosch Institute of Clinical Pharmacology 70376 Stuttgart Germany;University of Tuebingen 72074 Tuebingen Germany
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- 2022-10-26
- 2022
- English.
- In: Advanced Science. - : Wiley. - 2198-3844. ; , s. 2203368-2203368
- Journal article (peer-reviewed)
Abstract
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- Aberrant glucose homeostasis is the most common metabolic disturbance affecting one in ten adults worldwide. Prediabetic hyperglycemia due to dysfunctional interactions between different human tissues, including pancreas and liver, constitutes the largest risk factor for the development of type 2 diabetes. However, this early stage of metabolic disease has received relatively little attention. Microphysiological tissue models that emulate tissue crosstalk offer emerging opportunities to study metabolic interactions. Here, a novel modular multitissue organ-on-a-chip device is presented that allows for integrated and reciprocal communication between different 3D primary human tissue cultures. Precisely controlled heterologous perfusion of each tissue chamber is achieved through a microfluidic single “synthetic heart” pneumatic actuation unit connected to multiple tissue chambers via specific configuration of microchannel resistances. On-chip coculture experiments of organotypic primary human liver spheroids and intact primary human islets demonstrate insulin secretion and hepatic insulin response dynamics at physiological timescales upon glucose challenge. Integration of transcriptomic analyses with promoter motif activity data of 503 transcription factors reveals tissue-specific interacting molecular networks that underlie β-cell stress in prediabetic hyperglycemia. Interestingly, liver and islet cultures show surprising counter-regulation of transcriptional programs, emphasizing the power of microphysiological coculture to elucidate the systems biology of metabolic crosstalk.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Nanoteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Nano-technology (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Annan medicinteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Other Medical Engineering (hsv//eng)
Keyword
- glycemic control
- microfluidic cell culture
- microphysiological model
- organ-on-a-chip
- tissue interaction
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- art (subject category)
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