Alberta Diabetes Institute, Department of Surgery, 1-002 Li Ka Shing Centre for Health Research Innovation, University of Alberta, 112 St. NW & 87 Ave. NW, Edmonton, AB T6G 2E1, Canada.
Alberta Diabetes Institute, Department of Surgery, 1-002 Li Ka Shing Centre for Health Research Innovation, University of Alberta, 112 St. NW & 87 Ave. NW, Edmonton, AB T6G 2E1, Canada.
Cell Rep. 2022 Aug 23;40(8):111238. doi: 10.1016/j.celrep.2022.111238.
Recapitulation of embryonic pancreatic development has enabled development of methods for in vitro islet cell differentiation using human pluripotent stem cells (hPSCs), which have the potential to cure diabetes. Advanced methods for optimal generation of stem-cell-derived islets (SC-islets) has enabled successful diabetes reversal in rodents and shown promising early clinical trial outcomes. The main impediment for use of SC-islets is concern about safety because of off-target growth resulting from contaminated residual cells. In this review, we summarize the different endocrine and non-endocrine cell populations that have been described to emerge throughout β cell differentiation and after transplantation. We discuss the most recent approaches to enrich endocrine populations and remove off-target cells. Finally, we discuss the critical quality control and release criteria testing that we anticipate will be required prior to transplantation to ensure product safety.
胚胎胰腺发育的综述使得利用人类多能干细胞（hPSCs）进行体外胰岛细胞分化的方法得以发展，这有可能治愈糖尿病。优化干细胞衍生胰岛（SC-islets）生成的先进方法已在啮齿动物中实现了糖尿病的成功逆转，并显示出有希望的早期临床试验结果。使用 SC-islets 的主要障碍是对安全性的担忧，因为残留细胞的污染会导致非目标细胞的生长。在这篇综述中，我们总结了在β细胞分化过程中和移植后出现的不同内分泌和非内分泌细胞群体。我们讨论了最近用于富集内分泌细胞群和去除非目标细胞的方法。最后，我们讨论了在移植前预计需要进行的关键质量控制和放行标准测试，以确保产品的安全性。
