Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Ups J Med Sci. 2011 Mar;116(1):1-7. doi: 10.3109/03009734.2010.548609. Epub 2011 Feb 2.
Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early β-cell death increases the number of islets needed to restore glucose homeostasis. Moreover, late dysfunction and death contribute to the poor long-term results of islet transplantation on insulin independence. Studies in recent years have identified early and late challenges for transplanted pancreatic islets, including an instant blood-mediated inflammatory reaction when exposing human islets to the blood microenvironment in the portal vein and the low oxygenated milieu of islets transplanted into the liver. Poor revascularization of remaining intact islets combined with severe changes in the gene expression of islets transplanted into the liver contributes to late dysfunction. Strategies to overcome these hurdles have been developed, and some of these interventions are now even tested in clinical trials providing a hope to improve results in clinical islet transplantation. In parallel, experimental and clinical studies have, based on the identified problems with the liver site, evaluated the possibility of change of implantation organ in order to improve the results. Site-specific differences clearly exist in the engraftment of transplanted islets, and a more thorough characterization of alternative locations is needed. New strategies with modifications of islet microenvironment with cells and growth factors adhered to the islet surface or in a surrounding matrix could be designed to intervene with site-specific hurdles and provide possibilities to improve future results of islet transplantation.
胰岛移植到肝脏为治疗某些脆性 1 型糖尿病患者提供了一种可能。然而，大量的早期β细胞死亡增加了恢复葡萄糖稳态所需的胰岛数量。此外，胰岛的晚期功能障碍和死亡导致胰岛移植在胰岛素独立性方面的长期效果不佳。近年来的研究已经确定了移植胰岛的早期和晚期挑战，包括将人胰岛暴露于门静脉血液微环境时的即时血液介导的炎症反应，以及移植到肝脏的胰岛所处的低氧环境。剩余完整胰岛的血运重建不良，加上移植到肝脏的胰岛基因表达的严重变化，导致晚期功能障碍。已经开发出克服这些障碍的策略，其中一些干预措施甚至在临床试验中进行了测试，为改善临床胰岛移植的结果带来了希望。与此同时，实验和临床研究基于肝脏部位的发现问题，评估了改变植入器官的可能性，以改善结果。移植胰岛的植入部位存在明显的特异性差异，需要更彻底地描述替代部位。通过将细胞和生长因子附着在胰岛表面或周围基质上来修饰胰岛微环境的新策略，可以设计用来干预特定部位的障碍，并为改善胰岛移植的未来结果提供可能性。
