Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
Pancreas Islet Cell Research Center, Ankara Diskapi Yildirim Beyazit Training and Research Hospital Etlik Polyclinic, Department of Endocrinology and Metabolism, Ankara 06800, Turkey; Hacettepe University, School of Medicine, Department of Endocrinology, Ankara 06100, Turkey.
Acta Biomater. 2015 Aug;22:8-18. doi: 10.1016/j.actbio.2015.04.032. Epub 2015 Apr 27.
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.
胰岛移植是治疗 1 型糖尿病的一种有前途的方法。然而，由于完整性的丧失和血管网络的破坏，移植后胰岛的活力和功能受到限制。因此，提供一个适当的机械和生物支持环境对于提高体外胰岛培养和移植效率非常重要。在这里，我们证明肝素模拟肽两亲物（HM-PA）纳米纤维网络是实现这一目标的有前途的平台。与新鲜分离的胰岛相比，含有生长因子的肽纳米纤维凝胶培养的胰岛即使在 7 天后，其葡萄糖刺激指数也相似。将胰岛移植到 STZ 诱导的糖尿病大鼠后，28 天的监测显示，与仅胰岛移植组相比，在 HM-PA 纳米纤维凝胶中移植的胰岛能更好地将血糖维持在正常水平。此外，腹腔内葡萄糖耐量试验显示，在肽凝胶中移植胰岛的动物与健康对照组具有相似的模式。组织学评估表明，在肽纳米纤维凝胶中移植的胰岛由于血管密度增加，胰岛完整性更好。这项工作表明，使用 HM-PA 纳米纤维凝胶平台可以提高胰岛的功能和胰岛移植的效率，无论是在体外还是体内。
