Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic beta-cell differentiation in human embryonic stem cells |
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Authors: | Cho Young Min Lim Jung Mee Yoo Dae Hoon Kim Jae Hyeon Chung Sung Soo Park Sang Gyu Kim Tae Hyuk Oh Sun Kyung Choi Young Min Moon Shin Yong Park Kyong Soo Lee Hong Kyu |
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Affiliation: | a Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea b Department of Obstetrics and Gynecology, Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Republic of Korea |
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Abstract: | The major obstacle in cell therapy of diabetes mellitus is the limited source of insulin-producing β cells. Very recently, it was shown that a five-stage protocol recapitulating in vivo pancreatic organogenesis induced pancreatic β cells in vitro; however, this protocol is specific to certain cell lines and shows much line-to-line variation in differentiation efficacy. Here, we modified the five-stage protocol for the human embryonic stem cell line SNUhES3 by the addition of betacellulin and nicotinamide. We reproduced in vivo pancreatic islet differentiation by directing the cells through stages that resembled in vivo pancreatic organogenesis. The addition of betacellulin and nicotinamide sustained PDX1 expression and induced β-cell differentiation. C-peptide—a genuine marker of de novo insulin production—was identified in the differentiated cells, although the insulin mRNA content was very low. Further studies are necessary to develop more efficient and universal protocols for β-cell differentiation. |
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Keywords: | Embryonic stem cell Betacellulin Nicotinamide Insulin Pancreatic β cell |
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