Abstract：
Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β-cells. The prevailing treatment for T1DM involves daily subcutaneous insulin injections, but a substantial proportion of patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For T1DM patients, a more effective therapeutic option involves the replacement of β-cells through allogeneic transplantation of either the entire pancreas or isolated pancreatic islets. Unfortunately, the scarcity of transplantable human organs has led to a growing list of patients waiting for an islet transplant. One potential alternative is xenotransplantation of porcine pancreatic islets. However, due to inter-species molecular incompatibilities, porcine tissues trigger a robust immune response in humans, leading to xenograft rejection. Several promising strategies aim to overcome this challenge and enhance the long-term survival and functionality of xenogeneic islet grafts. These strategies include the use of islets derived from genetically modified pigs, immunoisolation of islets by encapsulation in biocompatible materials, and the creation of an immunomodulatory microenvironment by co-transplanting islets with accessory cells or utilizing immunomodulatory biomaterials. This review concentrates on delineating the primary obstacles in islet xenotransplantation and elucidates the fundamental principles and recent breakthroughs aimed at addressing these challenges.
摘要：
1型糖尿病（T1DM）的特征是绝对胰岛素缺乏，主要是由于胰腺β细胞的自身免疫破坏。T1DM的普遍治疗包括每日皮下注射胰岛素，但相当比例的患者面临严重的低血糖发作和控制不佳的高血糖等挑战.对于T1DM患者，更有效的治疗选择包括通过同种异体移植整个胰腺或分离的胰岛来替代β细胞.不幸的是,可移植的人体器官的匮乏导致越来越多的等待胰岛移植的患者名单。一种潜在的替代方法是猪胰岛的异种移植。然而,由于物种间的分子不相容性，猪组织在人类中引发强烈的免疫反应，导致异种移植排斥。几种有希望的策略旨在克服这一挑战并增强异种胰岛移植物的长期存活和功能。这些策略包括使用源自转基因猪的胰岛，通过封装在生物相容性材料中对胰岛进行免疫隔离，以及通过将胰岛与辅助细胞共同移植或利用免疫调节生物材料来创建免疫调节微环境。这篇综述集中于描述胰岛异种移植的主要障碍，并阐明了旨在解决这些挑战的基本原则和最新突破。
