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A Novel Subcutaneous Site of Islet Transplantation Superior to the Liver

Yasunami, Yohichi, MD1; Nakafusa, Yuki, MD2; Nitta, Naoyoshi, MS1; Nakamura, Masafumi, MD, PhD2; Goto, Masafumi, MD, PhD3; Ono, Junko, MD4; Taniguchi, Masaru, MD, PhD5

doi: 10.1097/TP.0000000000002162
Original Basic Science—General
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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 to 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 streptozotocin-induced diabetes in mice. Importantly, transplanted islets can be visualized by computed tomography and are easily retrievable, and allograft rejection is preventable by blockade of costimulatory 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.

Conclusions Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation.

The authors develop a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue in a mouse diabetic model. The new site of islet transplantation demonstrates high efficiency of attenuating hyperglycemia.

1 Islet Institute, Fukuoka University, Fukuoka, Japan.

2Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

3 Division of Transplantation and Regenerative Medicine, Tohoku University School of Medicine, Sendai, Japan.

4 Murakami Karindo Hospital, Fukuoka, Japan.

5 Laboratory for Immune Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.

Received 21 November 2017. Revision received 20 February 2018.

Accepted 24 February 2018.

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.).

The authors declare no conflicts of interest.

Y.Y. and M.T. designed the study, collected and analyzed the data, and wrote the article. 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.

Correspondence: Yohichi Yasunami, MD, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. (yasunami@fukuoka-u.ac.jp); Masaru Taniguchi, MD, PhD, 1-7-22, Suehiromachi, Tsurumi-ku, Yokohama 230-0045, Japan. (masaru.taniguchi@riken.jp).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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