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Survival and Metabolic Function of Syngeneic Mouse Islet Grafts Transplanted Into the Hepatic Sinus Tract

Li, Feng, MD1; Jiao, Ao, MD1; Li, Xiaohang, MD1; Zhang, Chengshuo, MD1; Sun, Ning, MD1; Zhang, Jialin, MD, PhD1

doi: 10.1097/TP.0000000000002289
Original Basic Science—General

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, after 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 longer than 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 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.

Islet grafts are transplanted into the liver via a portal vein but this method has several drawbacks. A hepatic sinus-tract (HST) was created by temporarily placing a medically approved cylindrical nylon rod into the hepatic parenchyma of C57BL/6 mice. Syngeneic islets placed in the HST control glycemia as islet grafts under the kidney capsule.

1 Hepatobiliary Surgery Department and Unit of Organ Transplantation, the First Hospital of China Medical University, Shenyang, China.

Received 22 January 2018. Revision received 18 April 2018.

Accepted 28 April 2018.

This work was supported by the National Natural Science Foundation of China (NSFC) (no. 31370989).

The authors declare no conflicts of interest.

F.L. participated in the research design, performance of the research, data analysis, and writing of the article. A.J., X.L., C.Z., and N.S. participated in the performance of the research and writing of the article. J.Z. participated in research design and writing of the manuscript.

Correspondence: Jialin Zhang, MD, PhD, Hepatobiliary Surgery Department and Unit of Organ Transplantation, the First Hospital of China Medical University, Shenyang 110001, China. (jlz2000@yeah.net).

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.