Survival and Metabolic Function of Syngeneic Mouse Islet Grafts Transplanted into the Hepatic Sinus-tract

Background Islet grafts are transplanted into the liver via a portal vein in 90% of the clinical islet transplantations. However, the portal vein is far from being the ideal infusion site due to its unique drawbacks. These issues necessitated the exploration of an alternatively optimized site for clinical islet transplantation. With the widespread clinical application of percutaneous transhepatic puncture technique, we envisioned the possibility of islet transplantation into the hepatic sinus-tract (HST). Methods The HST was created by temporarily placing a medically approved material into the hepatic parenchyma of C57BL/6 mice. The syngeneic islets were transplanted into the HST, following which, the nonfasting blood glucose, intraperitoneal glucose tolerance, and morphology were evaluated. Results A collagen-lined HST was formed by the 28-day implantation of a cylindrical nylon rod. Transplantation of ~300 syngeneic islets into the HST routinely reversed the hyperglycemia of the recipient mice and maintained normoglycemia for >100 days until the graft was removed. The islet grafts within the HST stained positively for insulin, glucagon, and abundant microvessels and achieved comparable results to the islet grafts under the kidney capsule (KC) with respect to glycemic control and glucose tolerance. Conclusions These results suggested that an HST can be constructed for islet transplantation by temporarily placing a nylon material in the liver parenchyma. The HST is a promising site for clinical islet transplantation, thereby providing a satisfactory environment for the survival and metabolic function of islet grafts. Corresponding author Jialin Zhang, MD, PhD, Hepatobiliary Surgery Department and Unit of Organ Transplantation, the First Hospital of China Medical University, Shenyang 110001, China. Tel: 86-24-83283310. Fax: 86-24-83282997. Email: jlz2000@yeah.net Contribution: F.L participated in the research design, performance of the research, data analysis and writing of the manuscript. A.J, X.L, C.Z and N.S participated in the performance of the research and writing of the manuscript. J.Z participated in research design and writing of the manuscript. Disclosure Statement The authors report no conflicts of interest and are solely responsible for the content and writing of this manuscript. Financial Support: This work was supported by the National Natural Science Foundation of China (NSFC) (no. 31370989). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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