Reprogramming human gallbladder cells into insulin-producing β-like cells.
Reprogramming human gallbladder cells into insulin-producing β-like cells.
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DOI：
10.1371/journal.pone.0181812
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Grompe M
中科院分区：
文献类型：
--
作者：
Galivo F;Benedetti E;Wang Y;Pelz C;Schug J;Kaestner KH;Grompe M
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro. The reprogrammed GBCs (rGBCs) strongly induced the production of insulin and pancreatic endocrine genes and these responded to glucose stimulation in vitro. rGBCs also expressed an islet-specific surface marker, which was used to enrich for the most highly reprogrammed cells. More importantly, global mRNA and microRNA expression profiles and protein immunostaining indicated that rGBCs adopted an overall β-like state and these rGBCs engrafted in immunodeficient mice. Furthermore, comparative global expression analyses identified putative regulators of human biliary to β cell fate conversion. In summary, we have developed, for the first time, a reliable and robust genetic reprogramming and culture expansion of primary human GBCs—derived from multiple unrelated donors—into pancreatic β-like cells ex vivo, thus showing that human gallbladder is a potentially rich source of reprogrammable cells for autologous cell therapy in diabetes.
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影响因子：
3.7
作者：
Chandra V;Swetha G;Muthyala S;Jaiswal AK;Bellare JR;Nair PD;Bhonde RR
通讯作者：
Bhonde RR
影响因子：
1.2
作者：
Dorrell, Craig;Abraham, Stephanie L.;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
158.5
作者：
Fioretto, P;Steffes, MW;Mauer, M
通讯作者：
Mauer, M
影响因子：
14.8
作者：
Chen, Shuibing;Borowiak, Malgorzata;Melton, Douglas
通讯作者：
Melton, Douglas
影响因子：
2.9
作者：
Gage, Blair K.;Riedel, Michael J.;Kieffer, Timothy J.
通讯作者：
Kieffer, Timothy J.