Wong Jordan M, Pepper Andrew R
Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Front Transplant. 2024 Nov 1;3:1485444. doi: 10.3389/frtra.2024.1485444. eCollection 2024.
Islet transplantation (ITx) is an effective means to restore physiologic glycemic regulation in those living with type 1 diabetes; however, there are a handful of barriers that prevent the broad application of this functionally curative procedure. The restricted cell supply, requisite for life-long toxic immunosuppression, and significant immediate and gradual graft attrition limits the procedure to only those living with brittle diabetes. While intraportal ITx is the primary clinical site, portal vein-specific factors including low oxygen tension and the instant blood-mediated inflammatory reaction are detrimental to initial engraftment and long-term function. These factors among others prevent the procedure from granting recipients long-term insulin independence. Herein, we provide an overview of the status and limitations of ITx, and novel innovations that address the shortcomings presented. Despite the marked progress highlighted in the review from as early as the initial islet tissue transplantation in 1893, ongoing efforts to improve the procedure efficacy and success are also explored. Progress in identifying unlimited cell sources, more favourable transplant sites, and novel drug delivery strategies all work to broaden ITx application and reduce adverse outcomes. Exploring combination of these approaches may uncover synergies that can further advance the field of ITx in providing sustainable functional cures. Finally, the potential of biomaterial strategies to facilitate immune evasion and local immune modulation are featured and may underpin successful application in alternative transplant sites.
胰岛移植（ITx）是恢复1型糖尿病患者生理血糖调节的有效手段；然而，有一些障碍阻碍了这种具有功能治愈性的手术的广泛应用。细胞供应受限、终身毒性免疫抑制的必要性以及显著的即刻和渐进性移植物损耗，使得该手术仅适用于脆性糖尿病患者。虽然门静脉内胰岛移植是主要的临床部位，但包括低氧张力和即时血液介导的炎症反应在内的门静脉特异性因素对初始植入和长期功能有害。这些因素以及其他因素使得该手术无法让接受者长期不依赖胰岛素。在此，我们概述了胰岛移植的现状和局限性，以及针对所呈现缺点的新创新。尽管早在1893年首次进行胰岛组织移植的综述中就强调了显著进展，但也探讨了为提高手术疗效和成功率而持续做出的努力。在确定无限细胞来源、更有利的移植部位和新型药物递送策略方面的进展，都有助于扩大胰岛移植的应用并减少不良后果。探索这些方法的组合可能会发现协同作用，从而进一步推动胰岛移植领域提供可持续的功能治愈。最后，重点介绍了生物材料策略促进免疫逃逸和局部免疫调节的潜力，这可能为在替代移植部位的成功应用奠定基础。
