A novel subcutaneous site of islet transplantation superior to the liver

AbstractBackgroundIslet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved.MethodsWe developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets. Also, it was determined whether islet allograft rejection in the ISWAT can be prevented by immunosuppressive agents. Furthermore, it was examined whether human islets function when grafted in this particular site of immune-deficient mice.ResultsIn this site, transplanted islets are engrafted as clusters and function to reverse STZ-induced diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much importance, the efficiency of islet transplantation in this site is superior to the liver, in which hyperglycemia of diabetic recipient mice is ameliorated after transplantation of 200 syngeneic islets (the islet number yielded from 1 mouse pancreas) to the ISWAT but not to the liver. Furthermore, human islets transplanted in this particular site function to reverse diabetes in immune-deficient mice.ConclusionThus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation. Background Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. Methods We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets. Also, it was determined whether islet allograft rejection in the ISWAT can be prevented by immunosuppressive agents. Furthermore, it was examined whether human islets function when grafted in this particular site of immune-deficient mice. Results In this site, transplanted islets are engrafted as clusters and function to reverse STZ-induced diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much importance, the efficiency of islet transplantation in this site is superior to the liver, in which hyperglycemia of diabetic recipient mice is ameliorated after transplantation of 200 syngeneic islets (the islet number yielded from 1 mouse pancreas) to the ISWAT but not to the liver. Furthermore, human islets transplanted in this particular site function to reverse diabetes in immune-deficient mice. Conclusion Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation. Correspondence: Yohichi Yasunami, MD, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. E-mail: yasunami@fukuoka-u.ac.jp; or Masaru Taniguchi, MD, PhD, 1-7-22, Suehiromachi, Tsurumi-ku, Yokohama 230-0045, Japan. E-mail: masaru.taniguchi@riken.jp Authorship Y.Y. and M.T. designed the study, collected and analysed data, and wrote the manuscript; Y.N. and N.N. participated in islet isolation and transplantation and the morphological studies; M.N., M.G. and J.O. participated in research design and data analysis. Disclosure: The authors declare no conflicts of interest. Funding: This work was supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities in Japan (S1512005) (Y.Y.) and by funds (No. 147014) from the Central Research Institute of Fukuoka University (Y.Y.). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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