Diabetes & Metabolism Journal

Original Articles

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; Korean Diabetes J. 2007;31(1):44-50. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.44

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Abstract PDF: BACKGROUND
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.

Activin A Converts Pancreatic Ductal Cells into Insulin-Secreting Cells.: Kyoung Hee Lee, Mi Kyung Park, Han Wook Kang, Hyun Jin Kim, In Kyung Jeong, Hyung Joon Yoo, Jae Hoon Jeong, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee; Korean Diabetes J. 2004;28(1):20-27. Published online February 1, 2004

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Abstract PDF: BACKGROUND
Islet transplantation as a potential treatment for diabetes has been investigated extensively over the past years. One of the major limitations to successful islet transplantation is shortage of insulin-producing tissue, which has stimulated the search for alternative sources, and recently, attention has been focused on the possible use of controlled differentiation of stem cells to obtain specialized cells useful in treating many diseases. It is currently believed that pancreatic progenitor or stem cells exist in the ductal cell population. Activin A is a member of the TGFbeta superfamily, which can block the exocrine pancreatic development and potentiate the endocrine development of the pancreas. In this study, whether activin A could expand and/or differentiate the ductal cells into insulin-producing cells was examined. METHODS: From a collagenase P digested pancreas, ductal tissue was cultured under conditions that allowed expansion as a monolayer, where the cells were overlaid with a rat tail collagen I-coated dish. Activin A cDNA was transfected into rat ductal cells by using Lipofectamine, and the insulin secretion, content and differentiation markers examined. RESULT: The clumps of ductal tissue adhered to the dish 24 hr later, and formed a complete monolayer after 3 days of culture. Activin A overexpression significantly increased both the insulin secretion and content from the ductal cells. The glucose(16.7mM)-induced insulin secretion was also significantly increased. Immunohistochemistry and RT-PCR analyses revealed expression of PDX-1, as well as insulin & GLUT2. CONCLUSION: Activin A overexpression could potentiate the differentiation of pancreatic ductal cells, which might provide a potential new source of cinsulin- producing cells for transplantation

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