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

Survival and Metabolic Function of Syngeneic Mouse Islet Grafts Transplanted Into the Hepatic Sinus Tract
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DOI:
10.1097/tp.0000000000002289
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发表时间:
2018-11-01
期刊:
影响因子:
6.2
通讯作者:
Zhang, Jialin
Zhang, Jialin
中科院分区:
医学2区
文献类型:
--
作者:
Li, Feng;Jiao, Ao;Zhang, Jialin

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背景在临床胰岛移植中,90%的胰岛移植物是通过门静脉移植到肝脏内的。然而,门静脉由于其独特的缺陷,远不是理想的输液部位。这些问题需要为临床胰岛移植寻找一种可供选择的优化部位。随着经皮肝穿技术在临床上的广泛应用,我们设想了将胰岛移植到肝窦道(HST)的可能性。将同种异体胰岛移植到HST内,观察移植后非空腹血糖、腹膜糖耐量及组织学变化。结果植入圆柱形尼龙棒28d后,HST形成胶原内衬。将接近300个同基因胰岛移植到HST中,通常可以逆转受体小鼠的高血糖,并保持正常血糖超过100天,直到移植物被移除。HST内的胰岛移植物胰岛素、胰升糖素和丰富的微血管染色呈阳性,在血糖控制和糖耐量方面与肾被膜下的胰岛移植物具有相似的结果。结论在肝实质内临时放置尼龙材料可以构建HST用于胰岛移植。HST是临床胰岛移植的理想场所,为胰岛移植物的存活和代谢功能提供了良好的环境。
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 similar to 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.