Shang Kuang-Ming, Suzuki Tomoharu, Kato Hiroyuki, Toyoda Taro, Tai Yu-Chong, Komatsu Hirotake
Department of Medical Engineering, California Institute of Technology, Pasadena, California, United States.
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Am J Physiol Cell Physiol. 2025 May 1;328(5):C1667-C1684. doi: 10.1152/ajpcell.00984.2024. Epub 2025 Apr 9.
Beta cell replacement therapy via pancreatic islet transplantation offers a promising treatment for type 1 diabetes as an alternative to insulin injections. However, posttransplantation oxygenation remains a critical challenge; isolated islets from donors lose vascularity and rely on slow oxygen diffusion for survival until revascularization occurs in the host tissue. This often results in significant hypoxia-induced acute graft loss. Overcoming the oxygenation barrier is crucial for advancing islet transplantation. This review is structured in three sections: the first examines oxygen dynamics in islet transplantation, focusing on factors affecting oxygen supply, including vascularity. It highlights oxygen dynamics specific to both transplant sites and islet grafts, with particular attention to extrahepatic sites such as subcutaneous tissue. The second section explores current oxygen delivery strategies, categorized into two main approaches: augmenting oxygen supply and enhancing effective oxygen solubility. The final section addresses key challenges, such as the lack of a clearly defined oxygen threshold for islet survival and the limited precision in measuring oxygen levels within small islet constructs. Recent advancements addressing these challenges are introduced. By deepening the understanding of oxygen dynamics and identifying current obstacles, this review aims to guide the development of innovative strategies for future research and clinical applications. These advancements are anticipated to enhance transplantation outcomes and bring us closer to a cure for type 1 diabetes.
通过胰岛移植进行的β细胞替代疗法为1型糖尿病提供了一种有前景的治疗方法，可替代胰岛素注射。然而，移植后的氧合作用仍然是一个关键挑战；来自供体的分离胰岛失去了血管，在宿主组织发生血管重建之前，它们依靠缓慢的氧扩散来维持生存。这常常导致严重的缺氧诱导的急性移植物丢失。克服氧合障碍对于推进胰岛移植至关重要。本综述分为三个部分：第一部分研究胰岛移植中的氧动力学，重点关注影响氧供应的因素，包括血管情况。它突出了移植部位和胰岛移植物特有的氧动力学，特别关注皮下组织等肝外部位。第二部分探讨当前的氧输送策略，分为两种主要方法：增加氧供应和提高有效氧溶解度。最后一部分讨论关键挑战，如缺乏明确界定的胰岛存活氧阈值以及在小胰岛结构内测量氧水平的精度有限。介绍了应对这些挑战的最新进展。通过加深对氧动力学的理解并识别当前的障碍，本综述旨在指导未来研究和临床应用中创新策略的开发。预计这些进展将改善移植结果，并使我们更接近治愈1型糖尿病。
