Generation of stem cell-derived β-cells from patients with type 1 diabetes

被引：261
|
作者：
Millman, Jeffrey R. [1 ,2 ]
Xie, Chunhui [3 ]
Van dervort, Alana [4 ]
Guertler, Mads [3 ]
Pagliuca, Felicia W. [5 ]
Melton, Douglas A. [3 ]
机构：
[1] Washington Univ, Div Endocrinol Metab & Lipid Res, Sch Med, Campus Box 8127,660 South Euclid Ave, St Louis, MO 63110 USA
[2] Washington Univ, Dept Biomed Engn, 1 Brookings Dr, St Louis, MO 63130 USA
[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, 7 Div Ave, Cambridge, MA 02138 USA
[4] Case Western Reserve Univ, Sch Med, 2109 Adelbert Rd, Cleveland, OH 44106 USA
[5] Semma Therapeut Inc, 450 Kendall St,Suite 2B, Cambridge, MA 02142 USA
来源：
NATURE COMMUNICATIONS | 2016年 / 7卷
关键词：
INSULIN-PRODUCING CELLS; IN-VITRO; PANCREATIC PROGENITORS; CANDIDATE GENES; MODEL; DIFFERENTIATION; MECHANISMS; ENDODERM; STRESS; ADULT;
D O I：
10.1038/ncomms11463
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
We recently reported the scalable in vitro production of functional stem cell-derived beta-cells (SC-beta cells). Here we extend this approach to generate the first SC-beta cells from type 1 diabetic patients (T1D). beta-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-beta cells express beta-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of b-cell stress. Using these assays, we find no major differences in T1D SC-beta cells compared with SC-beta cells derived from non-diabetic patients. These results show that T1D SC-beta cells could potentially be used for the treatment of diabetes, drug screening and the study of beta-cell biology.
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页数：8
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