Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States.
David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
Front Endocrinol (Lausanne). 2021 Sep 13;12:732431. doi: 10.3389/fendo.2021.732431. eCollection 2021.
Diabetes is a complex disease that affects over 400 million people worldwide. The life-long insulin injections and continuous blood glucose monitoring required in type 1 diabetes (T1D) represent a tremendous clinical and economic burdens that urges the need for a medical solution. Pancreatic islet transplantation holds great promise in the treatment of T1D; however, the difficulty in regulating post-transplantation immune reactions to avoid both allogenic and autoimmune graft rejection represent a bottleneck in the field of islet transplantation. Cell replacement strategies have been performed in hepatic, intramuscular, omentum, and subcutaneous sites, and have been performed in both animal models and human patients. However more optimal transplantation sites and methods of improving islet graft survival are needed to successfully translate these studies to a clinical relevant therapy. In this review, we summarize the current progress in the field as well as methods and sites of islet transplantation, including stem cell-derived functional human islets. We also discuss the contribution of immune cells, vessel formation, extracellular matrix, and nutritional supply on islet graft survival. Developing new transplantation sites with emerging technologies to improve islet graft survival and simplify immune regulation will greatly benefit the future success of islet cell therapy in the treatment of diabetes.
糖尿病是一种复杂的疾病，影响着全球超过 4 亿人。1 型糖尿病（T1D）患者需要终身注射胰岛素和持续监测血糖，这给他们带来了巨大的临床和经济负担，因此需要一种医疗解决方案。胰岛移植在 T1D 的治疗中具有广阔的前景；然而，调节移植后免疫反应以避免同种异体和自身免疫移植物排斥的困难，代表了胰岛移植领域的一个瓶颈。细胞替代策略已在肝、肌肉、大网膜和皮下等部位进行，并在动物模型和人类患者中进行。然而，需要更理想的移植部位和改善胰岛移植物存活的方法，才能将这些研究成功转化为临床相关的治疗方法。在这篇综述中，我们总结了该领域的最新进展，以及胰岛移植的方法和部位，包括干细胞衍生的功能性人胰岛。我们还讨论了免疫细胞、血管形成、细胞外基质和营养供应对胰岛移植物存活的贡献。利用新兴技术开发新的移植部位，以提高胰岛移植物的存活率和简化免疫调节，将极大地促进胰岛细胞治疗在糖尿病治疗中的未来成功。
