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Coculture With Ischemia/Reperfusion-Preconditioned Hepatocytes Improves Islet Function and Survival

Authors
 J.G. Lee  ;  J.I. Lee  ;  J.Y. Kim  ;  Y. Cho  ;  K.H. Huh  ;  B.S. Kim  ;  M.S. Kim  ;  Y.S. Kim  ;  D.J. Joo 
Citation
 Transplantation Proceedings, Vol.50(10) : 3887-3894, 2018 
Journal Title
 Transplantation Proceedings 
ISSN
 0041-1345 
Issue Date
2018
Abstract
In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-β1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion.
Full Text
https://www.sciencedirect.com/science/article/pii/S004113451830931X
DOI
10.1016/j.transproceed.2018.07.007
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김명수(Kim, Myoung Soo) ORCID logo https://orcid.org/0000-0002-8975-8381
김범석(Kim, Beom Seok) ORCID logo https://orcid.org/0000-0002-5732-2583
김유선(Kim, Yu Seun) ORCID logo https://orcid.org/0000-0002-5105-1567
이재근(Lee, Jae Geun) ORCID logo https://orcid.org/0000-0002-6722-0257
주동진(Joo, Dong Jin) ORCID logo https://orcid.org/0000-0001-8405-1531
허규하(Huh, Kyu Ha) ORCID logo https://orcid.org/0000-0003-1364-6989
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166869
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