Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Cells. 2020 Aug 31;9(9):1999. doi: 10.3390/cells9091999.
Islet cell transplantation is considered an ideal treatment for insulin-deficient diabetes, but implantation sites are limited and show low graft survival. Cell sheet technology and adipose-derived stem cells (ADSCs) can be useful tools for improving islet cell transplantation outcomes since both can increase implantation efficacy and graft survival. Herein, the optimal transplantation site in diabetic mice was investigated using islets and stem cell sheets. We constructed multi-layered cell sheets using rat/human islets and human ADSCs. Cell sheets were fabricated using temperature-responsive culture dishes. Islet/ADSC sheet (AI sheet) group showed higher viability and glucose-stimulated insulin secretion than islet-only group. Compared to islet transplantation alone, subcutaneous AI sheet transplantation showed better blood glucose control and CD31+ vascular traits. Because of the adhesive properties of cell sheets, AI sheets were easily applied on liver and peritoneal surfaces. Liver or peritoneal surface grafts showed better glucose control, weight gain, and intraperitoneal glucose tolerance test (IPGTT) profiles than subcutaneous site grafts using both rat and human islets. Stem cell sheets increased the therapeutic efficacy of islets in vivo because mesenchymal stem cells enhance islet function and induce neovascularization around transplanted islets. The liver and peritoneal surface can be used more effectively than the subcutaneous site in future clinical applications.
胰岛细胞移植被认为是治疗胰岛素缺乏型糖尿病的理想方法，但植入部位有限，移植物存活率低。细胞片技术和脂肪来源干细胞（ADSCs）可以成为改善胰岛细胞移植效果的有用工具，因为它们都可以提高植入效率和移植物存活率。在此，使用胰岛和干细胞片研究了糖尿病小鼠的最佳移植部位。我们使用大鼠/人胰岛和人 ADSCs 构建了多层细胞片。使用温度响应培养皿制备细胞片。胰岛/ADSC 片（AI 片）组的活力和葡萄糖刺激的胰岛素分泌均高于单纯胰岛组。与单独胰岛移植相比，皮下 AI 片移植显示出更好的血糖控制和 CD31+血管特征。由于细胞片的粘附特性，AI 片很容易应用于肝脏和腹膜表面。使用大鼠和人胰岛进行肝或腹膜表面移植的血糖控制、体重增加和腹腔内葡萄糖耐量试验（IPGTT）曲线均优于皮下部位。干细胞片增加了体内胰岛的治疗效果，因为间充质干细胞增强了胰岛功能，并诱导了移植胰岛周围的新血管生成。在未来的临床应用中，肝脏和腹膜表面可以比皮下部位更有效地使用。
