Targeted Derivation of Organotypic Glucose- and GLP-1-Responsive β Cells Prior to Transplantation into Diabetic Recipients.
发布时间：2023-02-27
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发表刊物：Stem Cell Reports
关键字：MAFA; NEUROG3; PDX1; iPSC; reprogramming; transcription factor; β-cell regeneration.
摘要：Generation of functional β cells from pluripotent sources would accelerate diagnostic and therapeutic applications for diabetes research and therapy. However, it has been challenging to generate competent β cells with dynamic insulin-secretory capacity to glucose and incretin stimulations. We introduced transcription factors, critical for β-cell development and function, in differentiating human induced pluripotent stem cells (PSCs) and assessed the impact on the functionality of derived β-cell (psBC) progeny. A perifusion system revealed stepwise transduction of the PDX1, NEUROG3, and MAFA triad (PNM) enabled in vitro generation of psBCs with glucose and GLP-1 responsiveness within 3 weeks. PNM transduction upregulated genes associated with glucose sensing, insulin secretion, and β-cell maturation. In recipient diabetic mice, PNM-transduced psBCs showed glucose-responsive insulin secretion as early as 1 week post transplantation. Thus, enhanced pre-emptive β-cell specification of PSCs by PNM drives generation of glucose- and incretin-responsive psBCs in vitro, offering a competent tissue-primed biotherapy.
合写作者：Tonne JM, Liu Q, Schreiber CA, Zhou Z, Rakshit K, Matveyenko AV, Terzic A, Wigle D, Kudva YC
第一作者：Zhu Y
论文类型：期刊论文
通讯作者：Ikeda Y
卷号：3
期号：(2)
页面范围：307-321
是否译文：否
发表时间：2019-08-13