Abstract
There is a need for physiologically relevant assay platforms to provide functionally relevant models of diabetes, to accelerate the discovery of new treatment options and boost developments in drug discovery. In this review, we compare several 3D-strategies that have been used to increase the functional relevance of ex vivo human primary pancreatic islets and developments into the generation of stem cell derived pancreatic beta-cells (β-cells). Special attention will be given to recent approaches combining the use of extracellular matrix (ECM) scaffolds with pancreatic molecular memory, which can be used to improve yield and functionality of in vitro stem cell-derived pancreatic models. The ultimate goal is to develop scalable cell-based platforms for diabetes research and drug screening. This article will critically assess key aspects related to in vitro pancreatic 3D-ECM models and highlight the most promising approaches for future research.
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Abbreviations
- DM:
-
Diabetes mellitus
- T1DM:
-
Type 1 diabetes mellitus
- T2DM:
-
Type 2 diabetes mellitus
- Islets:
-
Islets of Langerhans
- β-cells:
-
Beta-cells
- INS:
-
Insulin
- C-PEP:
-
C-Peptide
- GSIS:
-
Glucose-stimulated INS secretion
- ESCs:
-
Embryonic stem cell
- iPSC:
-
Induced pluripotent stem cell
- MSCs:
-
Mesenchymal stem cells
- ECM:
-
Extracellular matrix
- BM:
-
Basement membrane
- COL:
-
Collagen
- LN:
-
Laminin
- 3D:
-
3-dimensional
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DR is funded by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7 (2007–2013) under REA grant agreement n˚ [607842]. PW-S also acknowledge the Wallenberg Foundation, Chalmers Foundation and the Swedish Research Council.
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The authors declare a conflict of interest. DR, AK, RH and AF are employees and shareholders of AstraZeneca. PW-S is employed by Chalmers University of Technology and funded described in the acknowledge section. The funders did not have any role in the decision to publish or preparation of the manuscript.
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Ribeiro, D., Kvist, A.J., Wittung-Stafshede, P. et al. 3D-Models of Insulin-Producing β-Cells: from Primary Islet Cells to Stem Cell-Derived Islets. Stem Cell Rev and Rep 14, 177–188 (2018). https://doi.org/10.1007/s12015-017-9783-8
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DOI: https://doi.org/10.1007/s12015-017-9783-8