J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Department of Immunology and Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; University of Florida Diabetes Institute, Gainesville, FL, USA.
Adv Drug Deliv Rev. 2024 Mar;206:115179. doi: 10.1016/j.addr.2024.115179. Epub 2024 Jan 28.
Type 1 diabetes mellitus (T1DM) is an autoimmune condition that results in the destruction of insulin-secreting β cells of the islets of Langerhans. Allogeneic islet transplantation could be a successful treatment for T1DM; however, it is limited by the need for effective, permanent immunosuppression to prevent graft rejection. Upon transplantation, islets are rejected through non-specific, alloantigen specific, and recurring autoimmune pathways. Immunosuppressive agents used for islet transplantation are generally successful in inhibiting alloantigen rejection, but they are suboptimal in hindering non-specific and autoimmune pathways. In this review, we summarize the challenges with cellular immunological rejection and therapeutics used for islet transplantation. We highlight agents that target these three immune rejection pathways and how to package them for controlled, local delivery via biomaterials. Exploring macro-, micro-, and nano-scale immunomodulatory biomaterial platforms, we summarize their advantages, challenges, and future directions. We hypothesize that understanding their key features will help identify effective platforms to prevent islet graft rejection. Outcomes can further be translated to other cellular therapies beyond T1DM.
1 型糖尿病（T1DM）是一种自身免疫性疾病，导致胰岛的胰岛素分泌β细胞被破坏。同种异体胰岛移植可能是 T1DM 的一种成功治疗方法；然而，它受到有效、永久免疫抑制以防止移植物排斥的限制。移植后，胰岛通过非特异性、同种抗原特异性和复发性自身免疫途径被排斥。用于胰岛移植的免疫抑制剂通常成功地抑制同种抗原排斥，但在阻止非特异性和自身免疫途径方面效果不佳。在这篇综述中，我们总结了胰岛移植中细胞免疫排斥和治疗的挑战。我们强调了针对这三种免疫排斥途径的药物，以及如何通过生物材料对它们进行包装，以实现受控、局部递药。我们通过探索宏观、微观和纳米级免疫调节生物材料平台，总结了它们的优点、挑战和未来方向。我们假设，了解它们的关键特征将有助于确定有效的平台来预防胰岛移植物排斥。其结果还可以进一步转化为 T1DM 以外的其他细胞疗法。
