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一种使用生物可吸收医疗装置的新型皮下胰岛移植方法,以促进创建高度血管化的移植部位。

A novel subcutaneous islet transplantation method using a bioabsorbable medical device to facilitate the creation of a highly vascularized transplantation site.

作者信息

Emoto Norio, Anazawa Takayuki, Yamane Kei, Fujimoto Nanae, Murakami Takaaki, Fujimoto Hiroyuki, Jialin Cui, Ishida Satoshi, Kurahashi Kouki, Izuwa Aya, Su Hang, Inoguchi Kenta, Tada Seiichiro, Nagai Kazuyuki, Hatano Etsuro

机构信息

Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Institute for Life and Medical Sciences, Department of Regeneration Science and Engineering, Kyoto University, Kyoto, Japan.

出版信息

Cell Transplant. 2025 Jan-Dec;34:9636897251342986. doi: 10.1177/09636897251342986. Epub 2025 Jun 2.

Abstract

Subcutaneous transplantation is garnering attention as a potential transplantation site for pluripotent stem cell-derived islet cells to address the shortage of pancreatic islet transplant donors. However, subcutaneous transplantation of cells presents challenges related to angiogenesis, which is necessary for successful islet bioproduction. This study aimed to investigate a novel method for enhancing vascularization at the transplant site and thereby promote islet engraftment using a clinically available bioabsorbable medical device. A nonabsorbable device (agarose) or a bioabsorbable device (collagen-gelatin sheet [CGS]) loaded with basic fibroblast growth factor (bFGF) was implanted subcutaneously in C57BL/6 mice. There were two other groups of mice, one of which was implanted with CGS alone, which acted as a control, and another group that was implanted with bFGF-loaded agarose rods. Subsequently, 200 islets were transplanted into the subcutaneous pre-vascularized sites. An equivalent number of islets was also transplanted into the portal vein (IPTx) to compare transplantation efficacy. Vascularization of the graft site was evaluated before and after transplantation. bFGF significantly enhanced angiogenesis in the CGS mice. The normalization rate of blood glucose levels following islet transplantation in the bFGF-loaded CGS was group comparable to that in the bFGF-loaded agarose rod and IPTx groups. The presence of islets was confirmed using single-photon emission computed tomography (SPECT/CT), histological examination. Furthermore, it was noted that blood glucose levels rapidly increased after graft removal, showing that graft function was crucial to maintain normoglycemia. Importantly, the bFGF-loaded CGS showed a high rate of engraftment. This novel bioabsorbable medical device method exhibited remarkable efficacy in enhancing subcutaneous islet engraftment, potentially paving the way for a more straightforward and less invasive approach for islet cell transplantation in future clinical applications.

摘要

作为多能干细胞来源的胰岛细胞的潜在移植部位,皮下移植正受到关注,以解决胰岛移植供体短缺的问题。然而,细胞的皮下移植存在与血管生成相关的挑战,而血管生成对于成功的胰岛生物生产是必要的。本研究旨在研究一种新方法,通过使用临床可用的生物可吸收医疗设备来增强移植部位的血管化,从而促进胰岛植入。将负载碱性成纤维细胞生长因子(bFGF)的不可吸收设备(琼脂糖)或生物可吸收设备(胶原 - 明胶片[CGS])皮下植入C57BL/6小鼠体内。还有另外两组小鼠,其中一组单独植入CGS作为对照,另一组植入负载bFGF的琼脂糖棒。随后,将200个胰岛移植到皮下预先血管化的部位。还将等量的胰岛移植到门静脉(IPTx)中以比较移植效果。在移植前后评估移植部位的血管化情况。bFGF显著增强了CGS小鼠的血管生成。负载bFGF的CGS组胰岛移植后血糖水平的正常化率与负载bFGF的琼脂糖棒组和IPTx组相当。使用单光子发射计算机断层扫描(SPECT/CT)、组织学检查确认了胰岛的存在。此外,还注意到移植移除后血糖水平迅速升高,表明移植功能对于维持正常血糖至关重要。重要的是,负载bFGF的CGS显示出高植入率。这种新型生物可吸收医疗设备方法在增强皮下胰岛植入方面表现出显著效果,可能为未来临床应用中更直接、侵入性更小的胰岛细胞移植方法铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5512/12130648/b92f2c3f1eb9/10.1177_09636897251342986-img2.jpg

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