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

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作者
Jeffrey R. Millman
Chunhui Xie
Alana Van Dervort
Mads Gürtler
Felicia W. Pagliuca
Douglas A. Melton
机构
[1] Metabolism and Lipid Research,Division of Endocrinology
[2] Washington University School of Medicine,Department of Biomedical Engineering
[3] Campus Box 8127,Department of Stem Cell and Regenerative Biology
[4] 660 South Euclid Avenue,undefined
[5] St Louis,undefined
[6] Missouri 63110,undefined
[7] USA,undefined
[8] Washington University in St Louis,undefined
[9] 1 Brookings Drive,undefined
[10] St Louis,undefined
[11] Missouri 63130,undefined
[12] USA,undefined
[13] Harvard Stem Cell Institute,undefined
[14] Harvard University,undefined
[15] Case Western Reserve University School of Medicine,undefined
[16] Semma Therapeutics,undefined
[17] Inc.,undefined
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摘要
We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-β cells express β-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 β-cell stress. Using these assays, we find no major differences in T1D SC-β cells compared with SC-β cells derived from non-diabetic patients. These results show that T1D SC-β cells could potentially be used for the treatment of diabetes, drug screening and the study of β-cell biology.
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