For the past century, insulin injections have saved millions of lives, but glycemic instability is still a persistent challenge for people with diabetes, leading to tremendous morbidity and premature mortality. Research in the field of islet transplantation has demonstrated that replacing insulin-producing β cells can restore euglycemia comparable to individuals without diabetes. However, a short supply of cadaveric islet donors, the technically challenging process of isolating islets, and the requirement for chronic immune suppression have impeded widespread clinical adoption. Rather than relying on cadaveric cells, pluripotent stem cells could serve as a virtually unlimited supply of insulin-producing β cells. Protocols have been developed that mimic the normal in vivo development of the human pancreas to generate pancreatic progenitor cells in vitro. Ongoing investigations have yielded progressively more mature β-like cells in vitro that produce insulin but do not yet fully mimic healthy mature β cells. Alongside development of differentiation protocols, other work has provided insight into potential implantation sites for stem cell-derived islet cells including the subcutaneous space, portal vein, and omentum. To optimize implanted cell survival and function, development of immune modulation therapies is ongoing, including selection of immunomodulatory medications and genetic modification of implanted cells to evade immune responses. Further, macroencapsulation or microencapsulation devices could be used to contain and/or immunoprotect implanted cells from the immune response including by using 3-dimensional bioprinting to facilitate the process. Remarkably, ongoing clinical trials have now yielded the first patient relying on differentiated stem cells rather than syringes as their insulin replacement therapy.

中文翻译：

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从发现胰岛素到植入干细胞衍生胰岛的百年历程。

在过去的一个世纪里，胰岛素注射挽救了数百万人的生命，但血糖不稳定仍然是糖尿病患者面临的持续挑战，导致巨大的发病率和过早死亡。胰岛移植领域的研究表明，更换产生胰岛素的 β 细胞可以恢复与没有糖尿病的个体相当的正常血糖。然而，尸体胰岛供体的供应短缺、胰岛分离过程的技术挑战以及对慢性免疫抑制的要求阻碍了广泛的临床采用。多能干细胞不依赖于尸体细胞，而是可以几乎无限地供应产生胰岛素的 β 细胞。已经制定了模拟人胰腺正常体内发育以在体外产生胰腺祖细胞的方案。正在进行的研究已经在体外逐渐产生了更成熟的 β 样细胞，这些细胞产生胰岛素但尚未完全模仿健康的成熟 β 细胞。随着分化方案的发展，其他工作提供了对干细胞衍生胰岛细胞潜在植入部位的洞察力，包括皮下空间、门静脉和网膜。为了优化植入细胞的存活和功能，免疫调节疗法的开发正在进行中，包括免疫调节药物的选择和植入细胞的基因改造以逃避免疫反应。更远，宏观封装或微封装装置可用于包含和/或免疫保护植入细胞免受免疫反应，包括通过使用 3 维生物打印来促进该过程。值得注意的是，正在进行的临床试验现在已经产生了第一位依赖分化干细胞而不是注射器作为胰岛素替代疗法的患者。