Nanyang Institute of Technology in Health & Medicine, Interdisciplinary Graduate School, Nanyang Technological University, S639798, Singapore, Singapore.
School of Material Science and Engineering, Nanyang Technological University, S639798, Singapore, Singapore.
Sci Rep. 2019 Mar 8;9(1):3918. doi: 10.1038/s41598-019-40404-0.
The anterior chamber of the eye (ACE) has emerged as a promising clinical islet transplantation site because of its multiple advantages over the conventional intra-hepatic portal site. This includes reduced surgical invasiveness and increased islet graft survival rate. It also allows for enhanced accessibility and monitoring of the islets. Although the ACE is initially an immuno-privileged site, this privilege is disrupted once the islet grafts are re-vascularized. Given that the ACE is a confined space, achieving graft immune tolerance through local immunosuppressive drug delivery is therefore feasible. Here, we show that islet rejection in the ACE of mice can be significantly suppressed through local delivery of rapamycin by carefully designed sustained-release microparticles. In this 30-day study, allogeneic islet grafts with blank microparticles were completely rejected 18 days post-transplantation into mice. Importantly, allogeneic islet grafts co-injected with rapamycin releasing microparticles into a different eye of the same recipient were preserved much longer, with some grafts surviving for more than 30 days. Hence, islet allograft survival was enhanced by a localized and prolonged delivery of an immunosuppressive drug. We envisage that this procedure will relieve diabetic transplant recipients from harsh systemic immune suppression, while achieving improved glycemic control and reduced insulin dependence.
眼房水（ACE）已成为一种很有前途的临床胰岛移植部位，因为它相对于传统的肝内门静脉部位具有多个优势。这包括减少手术侵入性和提高胰岛移植物存活率。它还允许增强胰岛的可及性和监测。尽管 ACE 最初是一个免疫特权部位，但一旦胰岛移植物再血管化，这种特权就会被打破。鉴于 ACE 是一个封闭的空间，因此通过局部免疫抑制药物输送实现移植物免疫耐受是可行的。在这里，我们通过精心设计的缓释微球显示，局部递送雷帕霉素可显著抑制 ACE 中的胰岛排斥反应。在这项 30 天的研究中，在移植到小鼠后 18 天，用空白微球的同种异体胰岛移植物完全被排斥。重要的是，与共注射到同一受者的另一只眼的雷帕霉素释放微球的同种异体胰岛移植物保存时间更长，一些移植物存活超过 30 天。因此，通过局部和延长的免疫抑制药物输送增强了胰岛同种异体移植物的存活。我们设想，该程序将使糖尿病移植受者免受苛刻的全身免疫抑制，同时实现更好的血糖控制和减少胰岛素依赖。
