Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-0872, Japan.
Division of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Cells. 2023 Dec 26;13(1):51. doi: 10.3390/cells13010051.
Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group ( < 0.01). The cure rate was significantly higher in the GHNF group ( < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group ( < 0.01), and lectin angiography showed the same tendency ( < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group ( < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices.
虽然皮下胰岛移植具有许多优点,但除了在小鼠中,其在血管和移植效率方面在动物模型中仍较差。已提出使用两步法进行皮下胰岛移植,其中首先使用各种材料制备有利腔室,然后将胰岛移植到预制腔室中。我们之前报道了明胶水凝胶非织造布(GHNF)预处理的效果,并且预处理时间的长短会影响小鼠模型的结果。我们研究了 GHNF 预植入是否可以改善大鼠模型中的皮下胰岛移植结果。在胰岛移植前 3 周,将夹有硅树脂间隔物的 GHNF 片(GHNF 组)和没有 GHNF 片的硅树脂间隔物(对照组)植入受体的皮下空间,并在胰岛移植前 7 天诱导糖尿病。将同种异体胰岛移植到去除硅树脂间隔物的空间中。评估血糖水平、葡萄糖耐量、免疫组织化学和新生血管形成。与对照组相比,GHNF 组的血糖变化明显更好(<0.01)。GHNF 组的治愈率明显更高(<0.05)。GHNF 组的 vWF 阳性血管数量明显更多(<0.01),而 lectin 血管造影也显示出相同的趋势(<0.05)。移植胰岛周围的层粘连蛋白和胶原 III 的表达也在 GHNF 组中更高(<0.01)。GHNF 预处理在大鼠模型中是有效的,其主要机制可能是新生血管形成和细胞外基质的代偿。