Abstract
Type I diabetes results from the autoimmune destruction of the insulin-secreting pancreatic β-cells, affecting many millions of people worldwide. The optimal treatment is to restore the endogenous supply of insulin either through the transplantation of pancreas or the transplantation of islets of langerhans or simply the β-cells. However, the donated pancreas organs are limited and the available organs are only able to treat a small portion of the diabetes patients. Thus, glucose-responsive, insulin-producing cells from human origin are urgently needed. The aim of this chapter is to give some insight views to how to turn the potential human pancreatic non-endocrine cells into cells that are capable of secreting insulin in response to glucose and ameliorating insulin-deficient diabetes conditions after transplantation.
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References
Wang RN, Kloppel G, Bouwens L (1995) Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia. 38:1405–11.
Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE (1993) A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes. 42:1715–20.
Guz Y, Nasir I, Teitelman G (2001) Regeneration of pancreatic beta cells from intra-islet precursor cells in an experimental model of diabetes. Endocrinology 142: 4956–68.
Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature. 429:41–6.
Slack JM (1995) Developmental biology of the pancreas. Development. 121:1569–80.
Edlund H (1999) Pancreas: how to get there from the gut?. Curr Opin Cell Biol. 11:663–8.
Edlund H (1998). Transcribing pancreas. Dia-betes. 47:1817–23.
St-Onge L, Wehr R and Gruss P (1999) Pan-creas development and diabetes. Curr Opin Genet 9: 295–300.
von Schonfeld J, Goebell H, Muller MK (1994) The islet-acinar axis of the pancreas. Int J Pancreatol. 16:131–40.
Hall PA, Lemoine NR (1992) Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. J Pathol 166:97–103.
Githens S, Schexnayder JA, Moses RL, Denning GM, Smith JJ, Frazier ML (1994). Mouse pancreatic acinar/ductular tissue gives rise to epithelial cultures that are morphologically, biochemically, and functionally indistinguishable from interlobular duct cell cultures. In Vitro Cell Dev Biol Anim 30A:622–35.
Kerr-Conte J, Pattou F, Lecomte-Houcke M et al., (1996) Ductal cyst formation in collagen-embedded adult human islet preparations. A means to the reproduction of nesidioblastosis in vitro. Diabetes 45:1108–14.
Rooman I, Heremans Y, Heimberg H, Bouwens L (2000) Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro. Diabetologia 43:907–14.
Gmyr V, Kerr-Conte J, Belaich S et al., (2000) Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro: further evidence for pluripotent pancreatic stem cells in humans. Diabetes 49:1671–80.
Miller CP, McGehee RE Jr, Habener JF (1994) IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J. 13:1145–56.
Bonner-Weir S, Taneja M, Weir GC et al., (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA. 97:7999–8004.
Gao R, Ustinov J, Pulkkinen MA, Lundin K, Korsgren O, Otonkoski T (2003) Characteri-zation of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes. 52:2007–15.
Heremans Y, Van De Casteele M, in’t Veld P et al., (2002) Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3. J Cell Biol. 159:303–12.
Lardon J, Huyens N, Rooman I, Bouwens L (2004) Exocrine cell transdifferentiation in dexamethasone-treated rat pancreas. Virchows Arch. 444:61–5.
Baeyens L, De Breuck S, Lardon J, Mfopou J, K,Rooman I, Bouwens L. (2005) In vitro generation of insulin-producing cells from adult exocrine pancreatic cells. Diabetologia 48:49–57.
Hobbs S.M (1997) Artificial DNA; bicistronic eukaryotic expression vector pIRES-N1 submitted to EMBL/GenBank/DDBJ databases. AC no.: Y11035.
Zhao M, Amiel SA, Christie MR, Rela M, Heaton N, Huang GC. Insulin-producing cells derived from human pancreatic non-endocrine cell cultures reverse streptozotocin-induced hyperglycaemia in mice. Diabetologia. 2005 Oct; 48(10):2051–61.
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Zhao, M., Huang, G.C. (2012). Conversion of Non-endocrine Human Pancreatic Cells to Insulin-Producing Cells for Treatment of Diabetes. In: Mitry, R., Hughes, R. (eds) Human Cell Culture Protocols. Methods in Molecular Biology, vol 806. Humana Press. https://doi.org/10.1007/978-1-61779-367-7_6
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DOI: https://doi.org/10.1007/978-1-61779-367-7_6
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