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Matrix Biol. 2019 Jun 22. pii: S0945-053X(19)30149-0. doi: 10.1016/j.matbio.2019.06.008. [Epub ahead of print]

Non-invasive marker-independent high content analysis of a microphysiological human pancreas-on-a-chip model.

Author information

1
Dept. of Women's Health, Research Institute of Women's Health, Eberhard Karls University Tübingen, Germany.
2
Dept. of Women's Health, Research Institute of Women's Health, Eberhard Karls University Tübingen, Germany; The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany.
3
Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Stuttgart, Germany.
4
The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany.
5
Discipline of Anatomy and the Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Ireland; Science Foundation Ireland (SFI), Centre for Research in Advanced Materials for Biomedical Engineering (AMBER), Trinity College Dublin, National University of Ireland Galway, Galway, Ireland.
6
Dept. of Women's Health, Research Institute of Women's Health, Eberhard Karls University Tübingen, Germany; The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany; Dept. of Medicine/Cardiology, University of California Los Angeles (UCLA), Los Angeles, CA, USA. Electronic address: katja.schenke-layland@med.uni-tuebingen.de.
7
Dept. of Women's Health, Research Institute of Women's Health, Eberhard Karls University Tübingen, Germany; Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Stuttgart, Germany. Electronic address: peter.loskill@uni-tuebingen.de.

Abstract

The increasing prevalence of diabetes, its heterogeneity, and the limited number of treatment options drive the need for physiologically relevant assay platforms with human genetic background that have the potential to improve mechanistic understanding and e\xpedite diabetes-related research and treatment. In this study, we developed an endocrine pancreas-on-a-chip model based on a tailored microfluidic platform, which enables self-guided trapping of single human pseudo-islets. Continuous, low-shear perfusion provides a physiologically relevant microenvironment especially important for modeling and monitoring of the endocrine function as well as sufficient supply with nutrients and oxygen. Human pseudo-islets, generated from the conditionally immortalized EndoC-βH3 cell line, were successfully injected by hydrostatic pressure-driven flow without altered viability. To track insulin secretion kinetics in response to glucose stimulation in a time-resolved manner, dynamic sampling of the supernatant as well as non-invasive real-time monitoring using Raman microspectroscopy was established on-chip. Dynamic sampling indicated a biphasic glucose-stimulated insulin response. Raman microspectroscopy allowed to trace glucose responsiveness in situ and to visualize different molecular structures such as lipids, mitochondria and nuclei. In-depth spectral analyses demonstrated a glucose stimulation-dependent, increased mitochondrial activity, and a switch in lipid composition of insulin secreting vesicles, supporting the high performance of our pancreas-on-a-chip model.

KEYWORDS:

Diabetes; Insulin secretion; Organ-on-a-chip; Pancreatic islets; Raman imaging; Raman spectroscopy

PMID:
31238092
DOI:
10.1016/j.matbio.2019.06.008
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