Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Mol Ther. 2011 Oct;19(10):1759-68. doi: 10.1038/mt.2011.165. Epub 2011 Aug 9.
Embryonic stem cells (ESCs) harbor the potential to generate every cell type of the body by differentiation. The use of hESCs holds great promise for potential cell replacement therapies for degenerative diseases including diabetes mellitus. The recently discovered induced pluripotent stem cells (iPSCs) exhibit immense potential for regenerative medicine as they allow the generation of autologous cells tailored to the patients' immune system. Research for insulin-producing surrogate cells from ESCs has yielded highly controversial results, because many steps and factors in the differentiation process are currently still unknown. Thus, there is no consensus on common standard protocols. The protocols presently used established the differentiation from pluripotent cells toward pancreatic progenitor cells. However, none of the differentiation protocols reported to date have generated by exclusive in vitro differentiation sufficient numbers of insulin-producing cells meeting all essential criteria of a β-cell. The cells often lack the crucial function of regulated insulin secretion upon glucose stimulation. This review focuses on past and current approaches to the generation of insulin-producing cells from pluripotent sources, such as ESCs and iPSCs, and critically discusses the hurdles to be taken before insulin-secreting surrogate cells derived from these stem cells will be of clinical use in humans.
胚胎干细胞（ESCs）具有通过分化产生身体所有细胞类型的潜力。hESC 的应用为包括糖尿病在内的退行性疾病的潜在细胞替代疗法提供了巨大的希望。最近发现的诱导多能干细胞（iPSCs）在再生医学方面具有巨大的潜力，因为它们允许生成针对患者免疫系统的自体细胞。从 ESCs 中产生胰岛素分泌替代细胞的研究产生了极具争议的结果，因为分化过程中的许多步骤和因素目前仍不清楚。因此，关于通用标准方案没有共识。目前使用的方案从多能细胞分化为胰腺祖细胞。然而，迄今为止报道的任何分化方案都没有通过体外分化产生足够数量的满足β细胞所有基本标准的胰岛素分泌细胞。这些细胞通常缺乏在葡萄糖刺激下调节胰岛素分泌的关键功能。本综述重点介绍了过去和当前从多能细胞（如 ESCs 和 iPSCs）生成胰岛素分泌细胞的方法，并批判性地讨论了在这些干细胞衍生的胰岛素分泌替代细胞在人类中具有临床应用之前需要克服的障碍。
