Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Tissue Engineering and Hematology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Shahid Beheshti University of Medical Sciences, School of Advanced Technologies in Medicine, Tissue Engineering and Nanomedicine Research Center, Tehran, Iran.
Life Sci. 2021 Jun 1;274:119338. doi: 10.1016/j.lfs.2021.119338. Epub 2021 Mar 11.
Cell-based therapy is a promising approach for the treatment of type-1 diabetes mellitus. Identifying stem cells with differentiation potential to Insulin-producing cells (IPCs) and their application is an emerging issue. Different strategies have been used to support cell survival and their specific functions to control hyperglycemia conditions. Novel technologies using appropriate materials/fibers can improve cell transplantation.
In the present study, IPCs were differentiated from adipose-derived stem cells transduced with miR-375 and anti-miR-7. The cells' survival rate was also improved using a microfluidic system before their in vivo transplantation.
After adopting a stable, functional condition of the IPCs, the cells were used for in vivo grafting to diabetic mice, which resulted in a substantial drop in blood glucose during four weeks of grafting compared to the control group (p < 0.0001). The pattern of blood glucose levels in the mice receiving fiber entrapped IPCs, was similar to that of non-diabetic mice. Blood insulin was elevated in diabetic mice which received a transplant of fiber-entrapped-IPCs carrying miR-375 and anti-miR-7 after five weeks of transplantation compared to the diabetic mice (p < 0.014).
For the first time, this study showed that the two-component microfluidic system is useful for supporting the Collagen-Alginate fiber-entrapped IPCs and the miRNA-based cell therapy. Overall, our data show that the IPC encapsulation using a microfluidic system can support the cells in terms of morphology and biological function and their efficiency for controlling the hyperglycemia condition in diabetic mice.
细胞疗法是治疗 1 型糖尿病的一种很有前途的方法。鉴定具有向胰岛素分泌细胞（IPC）分化潜力的干细胞及其应用是一个新兴问题。已经使用了不同的策略来支持细胞的存活及其控制高血糖的特定功能。使用合适的材料/纤维的新技术可以改善细胞移植。
在本研究中，我们将 miR-375 和抗 miR-7 转导的脂肪来源干细胞分化为 IPC。还使用微流控系统在体内移植前提高细胞的存活率。
在 IPC 达到稳定、功能状态后，将细胞用于体内移植到糖尿病小鼠中，与对照组相比，移植后四周内血糖显著下降（p<0.0001）。接受纤维包埋 IPC 移植的小鼠的血糖水平模式与非糖尿病小鼠相似。在移植五周后，接受 miR-375 和抗 miR-7 携带纤维包埋 IPC 移植的糖尿病小鼠的血液胰岛素水平升高，与糖尿病小鼠相比（p<0.014）。
这是首次研究表明，双组份微流控系统有助于支持胶原-海藻酸盐纤维包埋的 IPC 和基于 miRNA 的细胞治疗。总体而言，我们的数据表明，使用微流控系统对 IPC 进行包封可以在形态和生物学功能方面支持细胞，并提高其控制糖尿病小鼠高血糖状态的效率。
