SHIMIZU Tatsuya    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Size effect of engineered islets prepared using microfabricated wells on islet cell function and arrangement.
Journal	Formal name：Heliyon Abbreviation：Heliyon ISSN code：(2405-8440)2405-8440(Linking)
Domestic / Foregin	Foregin
Publisher	Elsevier
Volume, Issue, Page	2(6),pp.e00129
Author and coauthor	ICHIHARA Yumie, UTOH Rie*, YAMADA Masumi, SHIMIZU Tatsuya, YASUKO UCHIGATA
Publication date	2016/06
Summary	Pancreatic islets are heterogeneous clusters mainly composed of α and β cells, and these clusters range in diameter from 50 to several hundred micrometers. Native small islets are known to have a higher insulin secretion ability in vitro and to provide better transplantation outcomes when compared with large islets. In this study, we prepared microengineered pseudo-islets from dispersed rat islet cells using precisely-fabricated agarose gel-based microwells with different diameters (100, 300, or 500 μm) to investigate the function and survival of islet cell aggregates with well-controlled sizes. We observed that dead cells were rarely present in the small pseudo-islets with an average diameter of ∼60 μm prepared using 100 μm microwells. In contrast, we observed more dead cells in the larger pseudo-islets prepared using 300 and 500 μm microwells. The relative amount of hypoxic cells was significantly low in the small pseudo-islets whereas a hypoxic condition was present in the core region of the larger pseudo-islets. In addition, we found that the small-sized pseudo-islets reconstituted the in vivo-tissue like arrangement of the α and β cells, and restored the high insulin secretory capacity in response to high glucose. These results clearly suggest that precise size control of pseudo-islets is essential for maintaining islet cell function and survival in vitro. The small-sized pseudo-islets may be advantageous for providing a better therapeutic approach for treating type 1 diabetes mellitus via islet reorganization and transplantation.
DOI	10.1016/j.heliyon.2016.e00129
PMID	27441299