Academic Journal

Bioengineered Pancreas–Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia

التفاصيل البيبلوغرافية
العنوان: Bioengineered Pancreas–Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia
المؤلفون: Reza Zandi Shafagh, Sonia Youhanna, Jibbe Keulen, Joanne X. Shen, Nayere Taebnia, Lena C. Preiss, Kathrin Klein, Florian A. Büttner, Mikael Bergqvist, Wouter van derWijngaart, Volker M. Lauschke
المصدر: Advanced Science, Vol 9, Iss 34, Pp n/a-n/a (2022)
بيانات النشر: Wiley, 2022.
سنة النشر: 2022
المجموعة: LCC:Science
مصطلحات موضوعية: glycemic control, microfluidic cell culture, microphysiological model, organ‐on‐a‐chip, tissue interaction, Science
الوصف: Abstract 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2198-3844
Relation: https://doaj.org/toc/2198-3844
DOI: 10.1002/advs.202203368
URL الوصول: https://doaj.org/article/657e83a29fa94ec4aab23e829d3d2254
رقم الانضمام: edsdoj.657e83a29fa94ec4aab23e829d3d2254
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:21983844
DOI:10.1002/advs.202203368