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Original Article Activin A and Glucose Derived Human Pancreatic Ductal Cells into Insulin-producing Cells.
Seung Hyun Hong, Chul Han, Hyo Sup Kim, Mi Kyung Park, Young Jin Lee, Jae Hoon Jeong, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee
Diabetes & Metabolism Journal 2007;31(1):44-50
Published online: January 1, 2007
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1Samsung Biomedical Research Institute (SBRI), Korea.
2Department of Life Science, College of Natural Sciences, Chungang University, Korea.
3Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea.

Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Human postnatal pancreatic ductal cells are a potential source of new beta cells. Therefore, we investigated the potential of human pancreatic ductal cells could be differentiated into endocrine cells that would be capable of secreting insulin in response to glucose. METHODS: Cell fractions enriched with pancreatic ductal cells after human islet isolation were treated with streptozotocin to remove residual beta cells, grown in monolayer culture, changed the media for differentiation in the presence of activin A and glucose, supplemented with 10% FCS. The differentiation markers, insulin secretion and cell proliferation were examined. RESULT: No insulin was detectable in cell preparations after 5 days of treatment with streptozotocin. In monolayer culture, 80% of the streptozotocin-treated pancreatic ductal cells expressed cytokeratin-19. Cell cultures with a high proportion of cytokeratin-19 cells had greater plasticity for differentiation into cells with phenotypic and functional markers of beta cells. This property were significantly enhanced by treatment of activin A and glucose. The differentiated human pancreatic ductal cells secreted insulin sensitively responded with high glucose. CONCLUSION: Human pancreatic ductal cells are a potential source of new glucose -induced insulin producing cells that may be developed further for clinical use. Therefore, the present data support a possible role for human adult pancreatic ductal cells, following expansion and differentiation, as a source of insulin by transplantation cells to type I diabetes patients.

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