1型糖尿病(T1DM)的特征是胰岛β细胞的损伤。细胞片工程,最新的治疗方法之一,还被用于通过创建胰岛/β细胞片并将这些系统转移到需要微创干预的区域来创建功能性胰岛系统,如肝外区域。因为胰岛,β细胞,胰腺移植是同种异体的,免疫问题,如组织排斥反应发生在治疗后,患者再次变得依赖胰岛素。在这项研究中,我们的目的是设计最适合的细胞片治疗方法和大胶囊装置,用于细胞片,可以在大鼠中提供长期的正常血糖。在这项研究中,我们开发了一种宏设备系统,该系统设计用于使用不同浓度的藻酸盐水凝胶将胰岛素输送到肝外移植部位。首先,将间充质干细胞(MSC)和β细胞在温度响应性培养皿中共培养以获得细胞片,然后在2%藻酸盐中进行大封装。表征了藻酸盐大胶囊装置的机械性能和孔径。在体外和体内评估了大胶囊中细胞片的活力和活性。空腹血糖水平,体重,在糖尿病大鼠移植后评估血清胰岛素和C肽水平。结果显示,第10天的血糖水平为225mg/dl,第15天的血糖水平为168mg/dl,移植后210天保持在正常血糖水平。在这项研究中,已经开发了一种藻酸盐大胶囊装置,以保护皮下移植后的细胞片免受免疫攻击,并允许移植物长时间发挥作用,作为未来T1DM患者胰岛移植的替代方法。我们的研究结果为未来的动物和人类研究提供了基础,在这些研究中,该方法可用于T1DM患者的长期细胞治疗。
Type 1 diabetes-mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule-device that could provide long-term normoglycemia in rats. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then the cell-sheets macroencapsulated using different concentrations of alginate. The mechanical properties and pore sizes of the macrocapsule-device were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluatedin vitroandin vivo. Fasting blood glucose levels, body weight, and serum insulin & C-peptide levels were evaluated after transplantation in diabetic-rats. After the transplantation, the blood glucose level at 225 mg dl-1on the 10th day dropped to 168 mg dl-1on the 15th day, and remained at the normoglycemic level for 210 days. In this study, an alginate macrocapsule-device was successfully developed to protect cell-sheets from immune attacks after transplantation. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.