Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA.
Nat Rev Endocrinol. 2010 Mar;6(3):139-48. doi: 10.1038/nrendo.2009.274.
The use of stem cells in regenerative medicine holds great promise for the cure of many diseases, including type 1 diabetes mellitus (T1DM). Any potential stem-cell-based cure for T1DM should address the need for beta-cell replacement, as well as control of the autoimmune response to cells which express insulin. The ex vivo generation of beta cells suitable for transplantation to reconstitute a functional beta-cell mass has used pluripotent cells from diverse sources, as well as organ-specific facultative progenitor cells from the liver and the pancreas. The most effective protocols to date have produced cells that express insulin and have molecular characteristics that closely resemble bona fide insulin-secreting cells; however, these cells are often unresponsive to glucose, a characteristic that should be addressed in future protocols. The use of mesenchymal stromal cells or umbilical cord blood to modulate the immune response is already in clinical trials; however, definitive results are still pending. This Review focuses on current strategies to obtain cells which express insulin from different progenitor sources and highlights the main pathways and genes involved, as well as the different approaches for the modulation of the immune response in patients with T1DM.
干细胞在再生医学中的应用为治疗许多疾病（包括 1 型糖尿病（T1DM））带来了巨大的希望。任何潜在的基于干细胞的 T1DM 治疗方法都应该解决β细胞替代的需求，以及控制对表达胰岛素的细胞的自身免疫反应。适合移植以重建功能性β细胞群的β细胞的体外生成已使用来自不同来源的多能细胞以及来自肝脏和胰腺的器官特异性兼性祖细胞。迄今为止最有效的方案已产生了表达胰岛素的细胞，并且其分子特征与真正的胰岛素分泌细胞非常相似；然而，这些细胞通常对葡萄糖无反应，这一特征在未来的方案中应该得到解决。使用间充质基质细胞或脐带血来调节免疫反应已经在临床试验中进行；然而，仍有待确定最终结果。本综述重点介绍了从不同祖细胞来源获得表达胰岛素的细胞的当前策略，并强调了涉及的主要途径和基因，以及用于调节 T1DM 患者免疫反应的不同方法。
