Diabetes mellitus is a pandemic metabolic disorder that results from either the autoimmune destruction or the dysfunction of insulin-producing pancreatic beta cells. A promising cure is beta cell replacement through the transplantation of islets of Langerhans. However, donor shortage hinders the widespread implementation of this therapy. Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, represent an attractive alternative beta cell source for transplantation. Although major advances over the past two decades have led to the generation of stem cell-derived beta-like cells that share many features with genuine beta cells, producing fully mature beta cells remains challenging. Here, we review the current status of beta cell differentiation protocols and highlight specific challenges that are associated with producing mature beta cells. We address the challenges and opportunities that are offered by monogenic forms of diabetes. Finally, we discuss the remaining hurdles for clinical application of stem cell-derived beta cells and the status of ongoing clinical trials.

中文翻译：

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使用干细胞衍生的β细胞实现糖尿病的功能性治疗：我们还存在吗？

糖尿病是由自身免疫破坏或产生胰岛素的胰岛β细胞功能障碍导致的大流行性代谢疾病。一种有希望的治疗方法是通过朗格罕氏岛的胰岛移植来替代β细胞。然而，供体短缺阻碍了该疗法的广泛实施。人多能干细胞，包括胚胎干细胞和诱导性多能干细胞，代表了一种有吸引力的可供移植的β细胞来源。尽管过去二十年来的重大进步导致了干细胞衍生的β样细胞的产生，它们与真正的β细胞具有许多功能，但生产完全成熟的β细胞仍然具有挑战性。这里，我们回顾了β细胞分化协议的当前状态，并重点介绍了与生产成熟β细胞相关的具体挑战。我们解决了单基因糖尿病所带来的挑战和机遇。最后，我们讨论了干细胞衍生的β细胞在临床上应用的剩余障碍以及正在进行的临床试验的现状。