Islet Transplantation Project, National Institute for Global Health and Medicine, Tokyo, Japan.
J Diabetes. 2020 Oct;12(10):733-741. doi: 10.1111/1753-0407.13041. Epub 2020 Apr 20.
Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but islet transplantation could make a type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non-heart-beating and living donors were used; in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donors are the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, although there is the risk of developing serious or novel infection. Therefore, the World Health Organization has been interested in xenotransplantation, and the International Xenotransplantation Association (IXA) has published consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently an efficient method to overcome xenorejection is an important research target. In addition to traditional immunosuppressive drugs and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once the xenorejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients.
目前，1 型糖尿病需要终身注射胰岛素和严格控制血糖以预防继发并发症，但胰岛移植可以使 1 型糖尿病患者摆脱胰岛素依赖。另一方面，胰岛移植需要人类供体，而供体短缺是最严重的问题。为了缓解供体短缺，使用了非心脏死亡和活体供体；此外，胰岛分离和移植的效果也得到了提高。然而，只要人类供体是唯一来源，供体短缺问题就不会得到解决。为了解决供体短缺问题，1994 年开始使用猪胰岛进行胰岛异种移植。尽管存在发生严重或新型感染的风险，但胰岛异种移植有治愈许多 1 型糖尿病患者的潜力。因此，世界卫生组织对异种移植很感兴趣，国际异种移植协会（IXA）已经发布了共识声明，以启动异种胰岛移植。临床胰岛异种移植在官方监管下进行，安全性和有效性数据已经积累。目前，克服异种排斥反应的有效方法是一个重要的研究目标。除了传统的免疫抑制药物和免疫隔离方法外，还研究了使用 CRISPR 和胚泡互补的基因修饰方法，取得了有希望的结果。一旦克服了异种排斥反应，胰岛异种移植应该成为 1 型糖尿病患者的一种治愈性治疗方法。
