Dhanasekaran Maheswaran, George Johnathan J, Loganathan Gopalakrishnan, Narayanan Siddharth, Hughes Michael G, Williams Stuart K, Balamurugan Appakalai N
Department of Surgery, Clinical Islet Cell Laboratory, Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA.
Curr Opin Organ Transplant. 2017 Oct;22(5):452-462. doi: 10.1097/MOT.0000000000000455.
The current article reviews the rationale, sources and preparation of pig islets for xenotransplantation, and presents current progress in solving the problems associated with establishing pig islet transplant as a clinical treatment for type 1 diabetes.
Islet transplantation is an effective treatment option for type 1 diabetes, but the available supply of human pancreases is insufficient to meet the need and demand for obtaining islets. Pig islets provide a readily available source for islet transplantation, with trials in non-human primates demonstrating their potential to reverse diabetes. The risk of zoonosis can be reduced by designated pathogen-free breeding of the donor pigs, but porcine endogenous retroviruses (PERVs) that are integrated into the genome of all pigs are especially difficult to eliminate. However, clinical trials have demonstrated an absence of PERV transmission with a significant reduction in the number of severe hypoglycemic episodes and up to 30% reduction in exogenous insulin doses. A number of methods such as production of various transgenic pigs to better xenotransplantation efficiency and the encapsulation of islets to isolate them from the host immune system are currently being tested to overcome the xenograft immune rejection. Furthermore, ongoing research is also shedding light on factors such as the age and breed of the donor pig to determine the optimal islet quantity and function.
本文回顾了用于异种移植的猪胰岛的基本原理、来源和制备方法,并介绍了在解决将猪胰岛移植确立为1型糖尿病临床治疗方法相关问题方面的当前进展。
胰岛移植是1型糖尿病的一种有效治疗选择,但人类胰腺的可用供应量不足以满足获取胰岛的需求。猪胰岛为胰岛移植提供了一个现成的来源,在非人类灵长类动物身上进行的试验证明了它们逆转糖尿病的潜力。通过对供体猪进行无特定病原体饲养,可以降低人畜共患病的风险,但整合到所有猪基因组中的猪内源性逆转录病毒(PERV)特别难以消除。然而,临床试验表明没有PERV传播,严重低血糖发作次数显著减少,外源性胰岛素剂量最多可降低30%。目前正在测试多种方法,如培育各种转基因猪以提高异种移植效率,以及封装胰岛以使其与宿主免疫系统隔离,以克服异种移植免疫排斥。此外,正在进行的研究也在揭示供体猪的年龄和品种等因素,以确定最佳的胰岛数量和功能。