Compact fluidic system for functional assessment of pancreatic islets
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Compact fluidic system for functional assessment of pancreatic islets Takeshi Hori 1
&
Kei Yamane 2 & Takayuki Anazawa 2 & Osamu Kurosawa 1 & Hiroo Iwata 1
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Transplantation of pancreatic islets is becoming a promising therapy for people with type I diabetes. In this study, we present a compact fluidic system that enables assessment of islet functionality ex vivo for efficient islet transplantation. The fluidic system includes a micromesh sheet-embedded chip. Islets can be loaded easily on the micromesh sheet and observed clearly by microscopy. Islets on the mesh sheet mainly remained in place during perfusion and did not get damaged by hydraulic pressure because of high porosity of the micromesh sheet. The fluidic system was assembled with a sample fraction chip of polydimethylsiloxane. The chip includes a channel and columns, both having surfaces that were super-hydrophilized so that solutions could flow smoothly within the chip by gravity. Using mouse pancreatic islets, a dynamic glucose-stimulated insulin secretion test was performed to examine the performance of the fluidic system. The system successfully analyzed levels and patterns of insulin secretion upon exposure of the islets to low- and high-glucose solutions in turns, thus demonstrating its capacity to assess islet functions more easily and cost-effectively. Keywords Pancreatic islets . Ex vivo analysis . Islet-on-a-chip . Fraction chip . Micromesh sheet
1 Introduction Diabetes is a chronic disease characterized by hyperglycemia, a condition characterized by excess amount of glucose in the blood (American Diabetes 2009). People living with diabetes numbered 425 million worldwide in 2017 and are estimated to rise to 629 million in 2045 (International Diabetes Federation 2017). Type 1 diabetes (T1D) accounts for 5–10% of diabetes cases (Maahs et al. 2010). It is characterized by the destruction of insulin-producing β cells present in the pancreatic islets. The destruction of β cells is mainly due to an autoimmune reaction, which results in the lack of insulin in the bloodstream, thus leading to hyperglycemia. Effective intervention to prevent T1D is currently not found. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10544-019-0443-4) contains supplementary material, which is available to authorized users. * Takeshi Hori [email protected] 1
Compass to Healthy Life Research Complex Program, RIKEN, 6-7-1 Minatojima-minamimachi, Chuou-ku, Kobe, Hyogo 650-0047, Japan
2
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, University of Kyoto, Kyoto, Japan
With the increasing incidence of T1D in the world (Maahs et al. 2010), transplantation of pancreatic islets is gaining importance as a treatment for T1D. The islets are about 50– 500 μm in diameter (Lenguito et al. 2017) and 3.6 × 106– 14.8 × 106 islets are distributed in the human pancreas (Saito et al. 1978)
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