Islet Institute, Fukuoka University, Fukuoka, Japan.
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Transplantation. 2018 Jun;102(6):945-952. doi: 10.1097/TP.0000000000002162.
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.
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.
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.
Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation.
胰岛移植是治疗胰岛素依赖型糖尿病患者的一种有吸引力的治疗方法，目前肝脏是首选的移植部位。然而，由于肝移植效率低，需要 2 到 3 个供体才能为单个受体提供供体，而且移植的胰岛无法进入或取出，因此需要寻找替代部位。
我们开发了一种将胰岛移植到小鼠腹股沟皮下白色脂肪组织（ISWAT）的新方法，并描述了同种异体胰岛移植的功能和形态特征。此外，还确定了免疫抑制剂是否可以预防 ISWAT 中胰岛同种异体移植排斥反应。此外，还研究了在这种免疫缺陷小鼠的特定部位移植人胰岛是否具有功能。
在该部位，移植的胰岛作为簇状结构被植入，并能逆转链脲佐菌素诱导的糖尿病。重要的是，通过计算机断层扫描可以观察到移植的胰岛，并且很容易取出，阻断共刺激信号可以预防同种异体移植排斥反应。更为重要的是，与肝脏相比，该部位胰岛移植的效率更高，在肝脏中，将 200 个同种异体胰岛（从 1 只老鼠胰腺中获得的胰岛数量）移植到 ISWAT 后可以改善糖尿病小鼠的高血糖，但不能移植到肝脏。此外，在该特定部位移植的人胰岛可以逆转免疫缺陷小鼠的糖尿病。
因此，ISWAT 优于肝脏作为胰岛移植的部位，这可能会改善临床胰岛移植的结果。
