Regeneration of pancreatic beta cells

Frontiers in Bioscience

Volumn 13, Issue 16, 2008, Pages 6170-6182

  Jun, Hee Sook ^a  

^a Gachon University College of Medicine   (South Korea)

Author keywords

Adult stem cell; Beta cell regeneration; Diabetes; Differentiation; Embryonic stem cell; Pancreatic islet; Progenitor cell; Review

Indexed keywords

TRANSCRIPTION FACTOR;

ANIMAL; BONE MARROW CELL; CELL DIFFERENTIATION; CELL DIVISION; CYTOLOGY; DIABETES MELLITUS; EMBRYONIC STEM CELL; HUMAN; INTESTINE; LIVER; METABOLISM; PANCREAS ISLET BETA CELL; PHYSIOLOGY; REGENERATION; REVIEW; TRANSPLANTATION;

ANIMALS; BONE MARROW CELLS; CELL DIFFERENTIATION; CELL DIVISION; DIABETES MELLITUS; EMBRYONIC STEM CELLS; HUMANS; INSULIN-SECRETING CELLS; INTESTINES; LIVER; REGENERATION; TRANSCRIPTION FACTORS;

EID: 52049084555     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/3145     Document Type: Article

References (151)

1. L. Adorini, S. Gregori, L. C. Harrison: Understanding autoimmune diabetes: insights from mouse models. Trends Mol Med 8, 31-38 (2002) (Pubitemid 34044676)
2. J. W. Yoon, H. S. Jun: Autoimmune destruction of pancreatic beta cells. Am J Ther 12, 580-591 (2005)
3. D. LeRoith: Beta-cell dysfunction and insulin resistance in type 2 diabetes: role of metabolic and genetic abnormalities. Am J Med 113 Suppl. 6A, 3S-11S (2002)
4. A. E. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, R. A. Rizza, P. C. Butler: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52, 102-110 (2003) (Pubitemid 36042113)
5. A. M. Shapiro, J. R. Lakey, E. A. Ryan, G. S. Korbutt, E. Toth, G. L. Warnock, N. M. Kneteman, R. V. Rajotte: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343, 230-238 (2000) (Pubitemid 30490390)
6. K. I. Rother, D. M. Harlan: Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus. J Clin Invest 114, 877-883 (2004) (Pubitemid 39578711)
7. B. Hatipoglu, E. Benedetti, J. Oberholzer: Islet transplantation: current status and future directions. Curr Diab Rep 5, 311-316 (2005) (Pubitemid 41269597)
8. L. C. Murtaugh, D. A. Melton: Genes, signals, and lineages in pancreas development. Annu Rev Cell Dev Biol 19, 71-89 (2003) (Pubitemid 37487343)
9. L. C. Murtaugh: Pancreas and beta-cell development: from the actual to the possible. Development 134, 427-438 (2007) (Pubitemid 46332480)
10. M. C. Jorgensen, J. Ahnfelt-Ronne, J. Hald, O. D. Madsen, P. Serup, J. Hecksher-Sorensen: An illustrated review of early pancreas development in the mouse. Endocr Rev 28, 685-705 (2007) (Pubitemid 47606652)
11. J. M. Wells, D. A. Melton: Vertebrate endoderm development. Annu Rev Cell Dev Biol 15, 393-410 (1999) (Pubitemid 32250381)
12. J. Dessimoz, R. Opoka, J. J. Kordich, A. Grapin-Botton, J. M. Wells: FGF signaling is necessary for establishing gut tube domains along the anterior-posterior axis in vivo. Mech Dev 123, 42-55 (2006) (Pubitemid 43031356)
13. V. A. McLin, S. A. Rankin, A. M. Zorn: Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development 134, 2207-2217 (2007) (Pubitemid 47010010)
14. J. Jensen: Gene regulatory factors in pancreatic development. Dev Dyn 229, 176-200 (2004) (Pubitemid 38036833)
15. M. Kanai-Azuma, Y. Kanai, J. M. Gad, Y. Tajima, C. Taya, M. Kurohmaru, Y. Sanai, H. Yonekawa, K. Yazaki, P. P. Tam, Y. Hayashi: Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 129, 2367-2379 (2002) (Pubitemid 34863845)
16. S. K. Kim, M. Hebrok, D. A. Melton: Notochord to endoderm signaling is required for pancreas development. Development 124, 4243-4252 (1997) (Pubitemid 27496860)
17. Y. Kawaguchi, B. Cooper, M. Gannon, M. Ray, R. J.MacDonald, C. V. Wright: The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 32, 128-134 (2002) (Pubitemid 34977207)
18. A. M. Holland, M. A. Hale, H. Kagami, R. E. Hammer, R. J. MacDonald: Experimental control of pancreatic development and maintenance. Proc Natl Acad Sci U S A 99, 12236-12241 (2002)
19. J. Hald, J. P. Hjorth, M. S. German, O. D. Madsen, P. Serup, J. Jensen: Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol 260, 426-437 (2003) (Pubitemid 36966084)
20. L. C. Murtaugh, B. Z. Stanger, K. M. Kwan, D. A. Melton: Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 100, 14920-14925 (2003) (Pubitemid 37517992)
21. A. Bhushan, N. Itoh, S. Kato, J. P. Thiery, P. Czernichow, S. Bellusci, R. Scharfmann: Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development 128, 5109-5117 (2001) (Pubitemid 34083036)
22. V. M. Schwitzgebel, D. W. Scheel, J. R. Conners, J. Kalamaras, J. E. Lee, D. J. Anderson, L. Sussel, J. D. Johnson, M. S. German: Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 127, 3533-3542 (2000)
23. G. Gu, J. Dubauskaite, D. A. Melton: Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129, 2447-2457 (2002) (Pubitemid 34863851)
24. A. Apelqvist, H. Li, L. Sommer, P. Beatus, D. J. Anderson, T. Honjo, M. Hrabe de Angelis, U. Lendahl, H. Edlund: Notch signalling controls pancreatic cell differentiation. Nature 400, 877-881 (1999) (Pubitemid 29406724)
25. P. A. Seymour, K. K. Freude, M. N. Tran, E. E. Mayes, J. Jensen, R. Kist, G. Scherer, M. Sander: SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci U S A 104, 1865-1870 (2007) (Pubitemid 46239870)
26. F. C. Lynn, S. B. Smith, M. E. Wilson, K. Y. Yang, N. Nekrep, M. S. German: Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci U S A 104, 10500-10505 (2007) (Pubitemid 47185694)
27. A. Krapp, M. Knofler, B. Ledermann, K. Burki, C. Berney, N. Zoerkler, O. Hagenbuchle, P. K. Wellauer: The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev 12, 3752-3763 (1998) (Pubitemid 29019655)
28. G. Gradwohl, A. Dierich, M. LeMeur, F. Guillemot: Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci U S A 97, 1607-1611 (2000) (Pubitemid 30118489)
29. L. Sussel, J. Kalamaras, D. J. Hartigan-O'Connor, J. J. Meneses, R. A. Pedersen, J. L. Rubenstein, M. S. German: Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells. Development 125, 2213-2221 (1998) (Pubitemid 28336383)
30. M. A. Cissell, L. Zhao, L. Sussel, E. Henderson, R. Stein: Transcription factor occupancy of the insulin gene in vivo. Evidence for direct regulation by Nkx2.2. J Biol Chem 278, 751-756 (2003) (Pubitemid 36790746)
31. B. Sosa-Pineda, K. Chowdhury, M. Torres, G. Oliver, P. Gruss: The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature 386, 399-402 (1997) (Pubitemid 27154480)
32. M. Sander, L. Sussel, J. Conners, D. Scheel, J. Kalamaras, F. Dela Cruz, V. Schwitzgebel, A. Hayes- Jordan, M. German: Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development 127, 5533-5540 (2000) (Pubitemid 32049205)
33. R. Ashery-Padan, X. Zhou, T. Marquardt, P. Herrera, L. Toube, A. Berry, P. Gruss: Conditional inactivation of Pax6 in the pancreas causes early onset of diabetes. Dev Biol 269, 479-488 (2004) (Pubitemid 38521112)
34. D. T. Finegood, L. Scaglia, S. Bonner-Weir: Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes 44, 249-256 (1995)
35. P. M. Davidson, I. L. Campbell, L. Oxbrow, J. M. Hutson, L. C. Harrison: Pancreatic beta cell proliferation in rabbits demonstrated by bromodeoxyuridine labeling. Pancreas 4, 594-600 (1989) (Pubitemid 19261028)
36. J. J. Meier, A. E. Butler, R. Galasso, R. A. Rizza, P. C. Butler: Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in humans. Diabetologia 49, 2689-2696 (2006) (Pubitemid 44510793)
37. K. Brennand, D. Huangfu, D. Melton: All beta cells contribute equally to islet growth and maintenance. PLoS Biol 5, e163 (2007)
38. Y. Dor, J. Brown, O. I. Martinez, D. A. Melton: Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429, 41-46 (2004) (Pubitemid 38620543)
39. C. J. Rhodes: Type 2 diabetes - a matter of beta-cell life and death? Science 307, 380-384 (2005) (Pubitemid 40139973)
40. R. L. Sorenson, T. C. Brelje: Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 29, 301-307 (1997) (Pubitemid 27293660)
41. L. C. Alonso, T. Yokoe, P. Zhang, D. K. Scott, S. K. Kim, C. P. O'Donnell, A. Garcia-Ocana: Glucose infusion in mice: a new model to induce beta-cell replication. Diabetes 56, 1792-1801 (2007) (Pubitemid 47025447)
42. G. M. Steil, N. Trivedi, J. C. Jonas, W. M. Hasenkamp, A. Sharma, S. Bonner-Weir, G. C. Weir: Adaptation of beta-cell mass to substrate oversupply: enhanced function with normal gene expression. Am J Physiol Endocrinol Metab 280, E788-796 (2001)
43. A. Garcia-Ocana, K. K. Takane, V. T. Reddy, J. C. Lopez-Talavera, R. C. Vasavada, A. F. Stewart: Adenovirus-mediated hepatocyte growth factor expression in mouse islets improves pancreatic islet transplant performance and reduces beta cell death. J Biol Chem 278, 343-351 (2003) (Pubitemid 36043582)
44. S. J. Brand, S. Tagerud, P. Lambert, S. G. Magil, K. Tatarkiewicz, K. Doiron, Y. Yan: Pharmacological treatment of chronic diabetes by stimulating pancreatic beta-cell regeneration with systemic co-administration of EGF and gastrin. Pharmacol Toxicol 91, 414-420 (2002) (Pubitemid 36132447)
45. M. A. Huotari, J. Palgi, T. Otonkoski: Growth factormediated proliferation and differentiation of insulinproducing INS-1 and RINm5F cells: identification of betacellulin as a novel beta-cell mitogen. Endocrinology 139, 1494-1499 (1998) (Pubitemid 28513801)
46. Y. Li, X. Cao, L. X. Li, P. L. Brubaker, H. Edlund, D. J. Drucker: Beta-cell pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Diabetes 54, 482-491 (2005)
47. T. Watanabe, Y. Yonemura, H. Yonekura, Y. Suzuki, H. Miyashita, K. Sugiyama, S. Moriizumi, M. Unno, O. Tanaka, H. Kondo, A. J. Bone, S. Takasawa, H. Okamoto: Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein. Proc Natl Acad Sci U S A 91, 3589-3592 (1994) (Pubitemid 24139475)
48. L. Rosenberg, M. Lipsett, J. W. Yoon, M. Prentki, R. Wang, H. S. Jun, G. L. Pittenger, D. Taylor-Fishwick, A. I. Vinik: A pentadecapeptide fragment of islet neogenesisassociated protein increases beta-cell mass and reverses diabetes in C57BL/6J mice. Ann Surg 240, 875-884 (2004) (Pubitemid 39425782)
49. J. Martin, S. L. Hunt, P. Dubus, R. Sotillo, F. Nehme- Pelluard, M. A. Magnuson, A. F. Parlow, M. Malumbres, S. Ortega, M. Barbacid: Genetic rescue of Cdk4 null mice restores pancreatic beta-cell proliferation but not homeostatic cell number. Oncogene 22, 5261-5269 (2003) (Pubitemid 37056088)
50. J. A. Kushner, M. A. Ciemerych, E. Sicinska, L. M. Wartschow, M. Teta, S. Y. Long, P. Sicinski, M. F. White: Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth. Mol Cell Biol 25, 3752-3762 (2005) (Pubitemid 40559580)
51. T. Uchida, T. Nakamura, N. Hashimoto, T. Matsuda, K. Kotani, H. Sakaue, Y. Kido, Y. Hayashi, K. I. Nakayama, M. F. White, M. Kasuga: Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med 11, 175-182 (2005) (Pubitemid 40321353)
52. J. Krishnamurthy, M. R. Ramsey, K. L. Ligon, C. Torrice, A. Koh, S. Bonner-Weir, N. E. Sharpless: p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443, 453-457 (2006) (Pubitemid 44477281)
53. E. Zeggini, M. N. Weedon, C. M. Lindgren, T. M. Frayling, K. S. Elliott, H. Lango, N. J. Timpson, J. R. Perry, N. W. Rayner, R. M. Freathy, J. C. Barrett, B. Shields, A. P. Morris, S. Ellard, C. J. Groves, L. W. Harries, J. L. Marchini, K. R. Owen, B. Knight, L. R. Cardon, M. Walker, G. A. Hitman, A. D. Morris, A. S. Doney, M. I. McCarthy, A. T. Hattersley: Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336-1341 (2007) (Pubitemid 46871654)
54. T. Xie, M. Chen, Q. H. Zhang, Z. Ma, L. S. Weinstein: Beta cell-specific deficiency of the stimulatory G protein alpha-subunit Gsalpha leads to reduced beta cell mass and insulin-deficient diabetes. Proc Natl Acad Sci U S A 104, 19601-19606 (2007)
55. I. C. Rulifson, S. K. Karnik, P. W. Heiser, D. ten Berge, H. Chen, X. Gu, M. M. Taketo, R. Nusse, M. Hebrok, S. K. Kim: Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci U S A 104, 6247-6252 (2007) (Pubitemid 47186080)
56. S. K. Karnik, C. M. Hughes, X. Gu, O. Rozenblatt- Rosen, G. W. McLean, Y. Xiong, M. Meyerson, S. K. Kim: Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27Kip1 and p18INK4c. Proc Natl Acad Sci U S A 102, 14659-14664 (2005) (Pubitemid 41457112)
57. R. W. Schnepp, Y. X. Chen, H. Wang, T. Cash, A. Silva, J. A. Diehl, E. Brown, X. Hua: Mutation of tumor suppressor gene Men1 acutely enhances proliferation of pancreatic islet cells. Cancer Res 66, 5707-5715 (2006) (Pubitemid 43927123)
58. D. Milo-Landesman, M. Surana, I. Berkovich, A. Compagni, G. Christofori, N. Fleischer, S. Efrat: Correction of hyperglycemia in diabetic mice transplanted with reversibly immortalized pancreatic beta cells controlled by the tet-on regulatory system. Cell Transplant 10, 645-650 (2001) (Pubitemid 34241692)
59. G. M. Beattie, P. Itkin-Ansari, V. Cirulli, G. Leibowitz, A. D. Lopez, S. Bossie, M. I. Mally, F. Levine, A. Hayek: Sustained proliferation of PDX-1+ cells derived from human islets. Diabetes 48, 1013-1019 (1999) (Pubitemid 29226347)
60. T. L. Halvorsen, G. Leibowitz, F. Levine: Telomerase activity is sufficient to allow transformed cells to escape from crisis. Mol Cell Biol 19, 1864-1870 (1999) (Pubitemid 29098244)
61. D. de la Tour, T. Halvorsen, C. Demeterco, B. Tyrberg, P. Itkin-Ansari, M. Loy, S. J. Yoo, E. Hao, S. Bossie, F. Levine: Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo. Mol Endocrinol 15, 476-483 (2001) (Pubitemid 32221923)
62. M. Narushima, N. Kobayashi, T. Okitsu, Y. Tanaka, S. A. Li, Y. Chen, A. Miki, K. Tanaka, S. Nakaji, K. Takei, A. S. Gutierrez, J. D. Rivas-Carrillo, N. Navarro- Alvarez, H. S. Jun, K. A. Westerman, H. Noguchi, J. R. Lakey, P. Leboulch, N. Tanaka, J. W. Yoon: A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol 23, 1274-1282 (2005) (Pubitemid 41486855)
63. J. Rajagopal, W. J. Anderson, S. Kume, O. I. Martinez, D. A. Melton: Insulin staining of ES cell progeny from insulin uptake. Science 299, 363 (2003) (Pubitemid 36120032)
64. M. Hansson, A. Tonning, U. Frandsen, A. Petri, J. Rajagopal, M. C. Englund, R. S. Heller, J. Hakansson, J. Fleckner, H. N. Skold, D. Melton, H. Semb, P. Serup: Artifactual insulin release from differentiated embryonic stem cells. Diabetes 53, 2603-2609 (2004) (Pubitemid 39299268)
65. B. Soria, E. Roche, G. Berna, T. Leon-Quinto, J. A. Reig, F. Martin: Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49, 157-162 (2000) (Pubitemid 30070992)
66. N. Lumelsky, O. Blondel, P. Laeng, I. Velasco, R. Ravin, R. McKay: Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292, 1389-1394 (2001) (Pubitemid 32476228)
67. Y. Hori, I. C. Rulifson, B. C. Tsai, J. J. Heit, J. D. Cahoy, S. K. Kim: Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci U S A 99, 16105-16110 (2002) (Pubitemid 35462756)
68. B. W. Kahan, L. M. Jacobson, D. A. Hullett, J. M. Ochoada, T. D. Oberley, K. M. Lang, J. S. Odorico: Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells: an in vitro model to study islet differentiation. Diabetes 52, 2016-2024 (2003) (Pubitemid 36919794)
69. P. Blyszczuk, J. Czyz, G. Kania, M. Wagner, U. Roll, L. St-Onge, A. M. Wobus: Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci U S A 100, 998-1003 (2003) (Pubitemid 36183944)
70. S. Miyazaki, E. Yamato, J. Miyazaki: Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. Diabetes 53, 1030-1037 (2004) (Pubitemid 38436615)
71. A. Shiroi, S. Ueda, Y. Ouji, K. Saito, K. Moriya, Y. Sugie, H. Fukui, S. Ishizaka, M. Yoshikawa: Differentiation of embryonic stem cells into insulinproducing cells promoted by Nkx2.2 gene transfer. World J Gastroenterol 11, 4161-4166 (2005) (Pubitemid 41086865)
72. T. Leon-Quinto, J. Jones, A. Skoudy, M. Burcin, B. Soria: In vitro directed differentiation of mouse embryonic stem cells into insulin-producing cells. Diabetologia 47, 1442-1451 (2004) (Pubitemid 39232431)
73. S. Assady, G. Maor, M. Amit, J. Itskovitz-Eldor, K. L. Skorecki, M. Tzukerman: Insulin production by human embryonic stem cells. Diabetes 50, 1691-1697 (2001) (Pubitemid 33641584)
74. H. Segev, B. Fishman, A. Ziskind, M. Shulman, J. Itskovitz-Eldor: Differentiation of human embryonic stem cells into insulin-producing clusters. Stem Cells 22, 265-274 (2004) (Pubitemid 38736611)
75. G. K. Brolen, N. Heins, J. Edsbagge, H. Semb: Signals from the embryonic mouse pancreas induce differentiation of human embryonic stem cells into insulin-producing etacell- like cells. Diabetes 54, 2867-2874 (2005) (Pubitemid 41401081)
76. H. T. Ku, N. Zhang, A. Kubo, R. O'Connor, M. Mao, G. Keller, J. S. Bromberg: Committing embryonic stem cells to early endocrine pancreas in vitro. Stem Cells 22, 1205-1217 (2004) (Pubitemid 39636399)
77. A. Kubo, K. Shinozaki, J. M. Shannon, V. Kouskoff, M. Kennedy, S. Woo, H. J. Fehling, G. Keller: Development of definitive endoderm from embryonic stem cells in culture. Development 131, 1651-1662 (2004) (Pubitemid 38559291)
78. M. Yasunaga, S. Tada, S. Torikai-Nishikawa, Y. Nakano, M. Okada, L. M. Jakt, S. Nishikawa, T. Chiba, T. Era: Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23, 1542-1550 (2005) (Pubitemid 41752932)
79. K. A. D'Amour, A. D. Agulnick, S. Eliazer, O. G. Kelly, E. Kroon, E. E. Baetge: Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23, 1534-1541 (2005) (Pubitemid 41752931)
80. K. A. D'Amour, A. G. Bang, S. Eliazer, O. G. Kelly, A. D. Agulnick, N. G. Smart, M. A. Moorman, E. Kroon, M. K. Carpenter, E. E. Baetge: Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24, 1392-1401 (2006) (Pubitemid 44722103)
81. J. Jiang, M. Au, K. Lu, A. Eshpeter, G. Korbutt, G. Fisk, A. S. Majumdar: Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25, 1940-1953 (2007) (Pubitemid 47258172)
82. W. Jiang, Y. Shi, D. Zhao, S. Chen, J. Yong, J. Zhang, T. Qing, X. Sun, P. Zhang, M. Ding, D. Li, H. Deng: In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res 17, 333-344 (2007) (Pubitemid 46639938)
83. I. S. Schroeder, A. Rolletschek, P. Blyszczuk, G. Kania, A. M. Wobus: Differentiation of mouse embryonic stem cells to insulin-producing cells. Nat Protoc 1, 495-507 (2006)
84. T. Fujikawa, S. H. Oh, L. Pi, H. M. Hatch, T. Shupe, B. E. Petersen: Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cellderived insulin-producing cells. Am J Pathol 166, 1781-1791 (2005) (Pubitemid 40734401)
85. S. Bonner-Weir, A. Sharma: Pancreatic stem cells. J Pathol 197, 519-526 (2002)
86. H. S. Jun, J. W. Yoon: Approaches for the cure of type 1 diabetes by cellular and gene therapy. Curr Gene Ther 5, 249-262 (2005)
87. E. Montanya: Islet- and stem-cell-based tissue engineering in diabetes. Curr Opin Biotechnol 15, 435-440 (2004) (Pubitemid 39304040)
88. T. Nir, Y. Dor: How to make pancreatic beta cells - prospects for cell therapy in diabetes. Curr Opin Biotechnol 16, 524-529 (2005) (Pubitemid 41393832)
89. D. Hess, L. Li, M. Martin, S. Sakano, D. Hill, B. Strutt, S. Thyssen, D. A. Gray, M. Bhatia: Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 21, 763-770 (2003) (Pubitemid 36791394)
90. V. Mathews, P. T. Hanson, E. Ford, J. Fujita, K. S. Polonsky, T. A. Graubert: Recruitment of bone marrowderived endothelial cells to sites of pancreatic beta-cell injury. Diabetes 53, 91-98 (2004) (Pubitemid 38044702)
91. H. Jahr, R. G. Bretzel: Insulin-positive cells in vitro generated from rat bone marrow stromal cells. Transplant Proc 35, 2140-2141 (2003) (Pubitemid 37194344)
92. L. B. Chen, X. B. Jiang, L. Yang: Differentiation of rat marrow mesenchymal stem cells into pancreatic islet betacells. World J Gastroenterol 10, 3016-3020 (2004) (Pubitemid 39303055)
93. C. Moriscot, F. de Fraipont, M. J. Richard, M. Marchand, P. Savatier, D. Bosco, M. Favrot, P. Y. Benhamou: Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells 23, 594-603 (2005) (Pubitemid 40478498)
94. O. Karnieli, Y. Izhar-Prato, S. Bulvik, S. Efrat: Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells 25, 2837-2844 (2007) (Pubitemid 350127868)
95. D. Q. Tang, L. Z. Cao, B. R. Burkhardt, C. Q. Xia, S. A. Litherland, M. A. Atkinson, L. J. Yang: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 53, 1721-1732 (2004) (Pubitemid 38857030)
96. A. Ianus, G. G. Holz, N. D. Theise, M. A. Hussain: In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111, 843-850 (2003) (Pubitemid 37074959)
97. J. B. Choi, H. Uchino, K. Azuma, N. Iwashita, Y. Tanaka, H. Mochizuki, M. Migita, T. Shimada, R. Kawamori, H. Watada: Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells. Diabetologia 46, 1366-1374 (2003) (Pubitemid 37297207)
98. A. Lechner, Y. G. Yang, R. A. Blacken, L. Wang, A. L. Nolan, J. F. Habener: No evidence for significant transdifferentiation of bone marrow into pancreatic betacells in vivo. Diabetes 53, 616-623 (2004) (Pubitemid 38270630)
99. T. D. Zorina, V. M. Subbotin, S. Bertera, A. M. Alexander, C. Haluszczak, B. Gambrell, R. Bottino, A. J. Styche, M. Trucco: Recovery of the endogenous beta cell function in the NOD model of autoimmune diabetes. Stem Cells 21, 377-388 (2003) (Pubitemid 36793482)
100. A. Pessina, B. Eletti, C. Croera, N. Savalli, C. Diodovich, L. Gribaldo: Pancreas developing markers expressed on human mononucleated umbilical cord blood cells. Biochem Biophys Res Commun 323, 315-322 (2004) (Pubitemid 39200684)
101. Y. Zhao, H. Wang, T. Mazzone: Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics. Exp Cell Res 312, 2454-2464 (2006) (Pubitemid 44036799)
102. B. Sun, K. H. Roh, S. R. Lee, Y. S. Lee, K. S. Kang: Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. Biochem Biophys Res Commun 354, 919-923 (2007) (Pubitemid 46216220)
103. A. Grapin-Botton, D. A. Melton: Endoderm development: from patterning to organogenesis. Trends Genet 16, 124-130 (2000) (Pubitemid 30122350)
104. L. Yang, S. Li, H. Hatch, K. Ahrens, J. G. Cornelius, B. E. Petersen, A. B. Peck: In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormoneproducing cells. Proc Natl Acad Sci U S A 99, 8078-8083 (2002) (Pubitemid 34651008)
105. L. Z. Cao, D. Q. Tang, M. E. Horb, S. W. Li, L. J. Yang: High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 53, 3168-3178 (2004) (Pubitemid 39564492)
106. M. Zalzman, S. Gupta, R. K. Giri, I. Berkovich, B. S. Sappal, O. Karnieli, M. A. Zern, N. Fleischer, S. Efrat: Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. Proc Natl Acad Sci U S A 100, 253-7258 (2003)
107. N. Nakajima-Nagata, T. Sakurai, T. Mitaka, T. Katakai, E. Yamato, J. Miyazaki, Y. Tabata, M. Sugai, A. Shimizu: In vitro induction of adult hepatic progenitor cells into insulin-producing cells. Biochem Biophys Res Commun 318, 625-630 (2004) (Pubitemid 38624199)
108. T. Sapir, K. Shternhall, I. Meivar-Levy, T. Blumenfeld, H. Cohen, E. Skutelsky, S. Eventov-Friedman, I. Barshack, I. Goldberg, S. Pri-Chen, L. Ben-Dor, S. Polak-Charcon, A. Karasik, I. Shimon, E. Mor, S. Ferber: Cell-replacement therapy for diabetes: Generating functional insulinproducing tissue from adult human liver cells. Proc Natl Acad Sci U S A 102, 7964-7969 (2005) (Pubitemid 40781046)
109. S. Ferber, A. Halkin, H. Cohen, I. Ber, Y. Einav, I. Goldberg, I. Barshack, R. Seijffers, J. Kopolovic, N. Kaiser, A. Karasik: Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 6, 568-572 (2000) (Pubitemid 30305908)
110. H. Kojima, M. Fujimiya, K. Matsumura, P. Younan, H. Imaeda, M. Maeda, L. Chan: NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 9, 596-603 (2003) (Pubitemid 36597107)
111. H. Kojima, T. Nakamura, Y. Fujita, A. Kishi, M. Fujimiya, S. Yamada, M. Kudo, Y. Nishio, H. Maegawa, M. Haneda, H. Yasuda, I. Kojima, M. Seno, N. C. Wong, R. Kikkawa, A. Kashiwagi: Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin. Diabetes 51, 1398-1408 (2002) (Pubitemid 34826605)
112. S. Yoshida, Y. Kajimoto, T. Yasuda, H. Watada, Y. Fujitani, H. Kosaka, T. Gotow, T. Miyatsuka, Y. Umayahara, Y. Yamasaki, M. Hori: PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulinproducing cells. Diabetes 51, 2505-2513 (2002) (Pubitemid 34827400)
113. A. Suzuki, H. Nakauchi, H. Taniguchi: Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells. Proc Natl Acad Sci U S A 100, 5034-5039 (2003) (Pubitemid 36542653)
114. Y. Hori, X. Gu, X. Xie, S. K. Kim: Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2, e103 (2005)
115. J. J. Meier, A. Bhushan, A. E. Butler, R. A. Rizza, P. C. Butler: Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia 48, 2221-2228 (2005) (Pubitemid 41618910)
116. S. Bonner-Weir, L. A. Baxter, G. T. Schuppin, F. E. Smith: A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes 42, 1715-1720 (1993) (Pubitemid 23346407)
117. V. K. Ramiya, M. Maraist, K. E. Arfors, D. A. Schatz, A. B. Peck, J. G. Cornelius: Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6, 278-282 (2000) (Pubitemid 30148619)
118. S. Bonner-Weir, M. Taneja, G. C. Weir, K. Tatarkiewicz, K. H. Song, A. Sharma, J. J. O'Neil: In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97, 7999-8004 (2000) (Pubitemid 30460762)
119. S. Bonner-Weir, A. Sharma: Are there pancreatic progenitor cells from which new islets form after birth? Nat Clin Pract Endocrinol Metab 2, 240-241 (2006)
120. X. Xu, J. D'Hoker, G. Stange, S. Bonne, N. De Leu, X. Xiao, M. Van De Casteele, G. Mellitzer, Z. Ling, D. Pipeleers, L. Bouwens, R. Scharfmann, G. Gradwohl, H. Heimberg: Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132, 197-207 (2008) (Pubitemid 351181232)
121. R. M. Seaberg, S. R. Smukler, T. J. Kieffer, G. Enikolopov, Z. Asghar, M. B. Wheeler, G. Korbutt, D. Van Der Kooy: Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22, 1115-1124 (2004) (Pubitemid 39166849)
122. H. Taniguchi, E. Yamato, F. Tashiro, H. Ikegami, T. Ogihara, J. Miyazaki: Beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 10, 15-23 (2003) (Pubitemid 36175822)
123. H. Noguchi, H. Kaneto, G. C. Weir, S. Bonner-Weir: PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells. Diabetes 52, 1732-1737 (2003) (Pubitemid 36792464)
124. W. L. Suarez-Pinzon, J. R. Lakey, S. J. Brand, A. Rabinovitch: Combination therapy with epidermal growth factor and gastrin induces neogenesis of human islet {beta}-cells from pancreatic duct cells and an increase in functional {beta}-cell mass. J Clin Endocrinol Metab 90, 3401-3409 (2005) (Pubitemid 41014304)
125. I. Rooman, L. Bouwens: Combined gastrin and epidermal growth factor treatment induces islet regeneration and restores normoglycaemia in C57Bl6/J mice treated with alloxan. Diabetologia 47, 259-265 (2004) (Pubitemid 38315362)
126. K. Minami, M. Okuno, K. Miyawaki, A. Okumachi, K. Ishizaki, K. Oyama, M. Kawaguchi, N. Ishizuka, T. Iwanaga, S. Seino: Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci U S A 102, 15116-15121 (2005) (Pubitemid 41513344)
127. L. Baeyens, S. De Breuck, J. Lardon, J. K. Mfopou, I. Rooman, L. Bouwens: In vitro generation of insulinproducing beta cells from adult exocrine pancreatic cells. Diabetologia 48, 49-57 (2005) (Pubitemid 40174656)
128. L. Baeyens, S. Bonne, M. S. German, P. Ravassard, H. Heimberg, L. Bouwens: Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway. Cell Death Differ 13, 1892-1899 (2006) (Pubitemid 44542402)
129. A. Lechner, A. L. Nolan, R. A. Blacken, J. F. Habener: Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue. Biochem Biophys Res Commun 327, 581-588 (2005) (Pubitemid 40040514)
130. E. Hao, B. Tyrberg, P. Itkin-Ansari, J. R. Lakey, I. Geron, E. Z. Monosov, M. Barcova, M. Mercola, F. Levine: Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas. Nat Med 12, 310-316 (2006) (Pubitemid 43355079)
131. S. Kodama, W. Kuhtreiber, S. Fujimura, E. A. Dale, D. L. Faustman: Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 302, 1223-1227 (2003) (Pubitemid 37421029)
132. A. Suri, B. Calderon, T. J. Esparza, K. Frederick, P. Bittner, E. R. Unanue: Immunological reversal of autoimmune diabetes without hematopoietic replacement of beta cells. Science 311, 1778-1780 (2006)
133. J. Nishio, J. L. Gaglia, S. E. Turvey, C. Campbell, C. Benoist, D. Mathis: Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution. Science 311, 1775-1778 (2006)
134. A. S. Chong, J. Shen, J. Tao, D. Yin, A. Kuznetsov, M. Hara, L. H. Philipson: Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell regeneration. Science 311, 1774-1775 (2006)
135. Y. Hisatomi, K. Okumura, K. Nakamura, S. Matsumoto, A. Satoh, K. Nagano, T. Yamamoto, F. Endo: Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages.
136. K. Timper, D. Seboek, M. Eberhardt, P. Linscheid, M. Christ-Crain, U. Keller, B. Muller, H. Zulewski: Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagons expressing cells. Biochem Biophys Res Commun 341, 1135-1140 (2006) (Pubitemid 43221783)
137. J. P. Wei, T. S. Zhang, S. Kawa, T. Aizawa, M. Ota, T. Akaike, K. Kato, I. Konishi, T. Nikaido: Human amnionisolated cells normalize blood glucose in streptozotocininduced diabetic mice. Cell Transplant 12, 545-552 (2003) (Pubitemid 36993198)
138. C. J. Burns, S. L. Minger, S. Hall, H. Milne, R. D. Ramracheya, N. D. Evans, S. J. Persaud, P. M. Jones: The in vitro differentiation of rat neural stem cells into an insulin-expressing phenotype. Biochem Biophys Res Commun 326, 570-577 (2005) (Pubitemid 39642762)
139. M. Ruhnke, H. Ungefroren, A. Nussler, F. Martin, M. Brulport, W. Schormann, J. G. Hengstler, W. Klapper, K. Ulrichs, J. A. Hutchinson, B. Soria, R. M. Parwaresch, P. Heeckt, B. Kremer, F. Fandrich: Differentiation of in vitromodified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 128, 1774-1786 (2005) (Pubitemid 40824688)
140. K. Yamamoto, J. Miyagawa, M. Waguri, R. Sasada, K. Igarashi, M. Li, T. Nammo, M. Moriwaki, A. Imagawa, K. Yamagata, H. Nakajima, M. Namba, Y. Tochino, T. Hanafusa, Y. Matsuzawa: Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion. Diabetes 49, 2021-2027 (2000)
141. L. Li, M. Seno, H. Yamada, I. Kojima: Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to beta-cells in streptozotocintreated mice. Am J Physiol Endocrinol Metab 285, E577- 583 (2003) (Pubitemid 37010836)
142. L. Li, M. Seno, H. Yamada, I. Kojima: Promotion of beta-cell regeneration by betacellulin in ninety percentpancreatectomized rats. Endocrinology 142, 5379-5385 (2001) (Pubitemid 33131971)
143. W. L. Suarez-Pinzon, Y. Yan, R. Power, S. J. Brand, A. Rabinovitch: Combination therapy with epidermal growth factor and gastrin increases beta-cell mass and reverses hyperglycemia in diabetic NOD mice. Diabetes 54, 2596-2601 (2005) (Pubitemid 41233580)
144. L. Li, Z. Yi, M. Seno, I. Kojima: Activin A and betacellulin: effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats. Diabetes 53, 608-615 (2004) (Pubitemid 38270629)
145. N. Ogawa, J. F. List, J. F. Habener, T. Maki: Cure of overt diabetes in NOD mice by transient treatment with anti-lymphocyte serum and exendin-4. Diabetes 53, 1700-1705 (2004) (Pubitemid 38857027)
146. M. J. Liu, S. Shin, N. Li, T. Shigihara, Y. S. Lee, J. W. Yoon, H. S. Jun: Prolonged remission of diabetes by regeneration of beta cells in diabetic mice treated with recombinant adenoviral vector expressing glucagon-like peptide-1. Mol Ther 15, 86-93 (2007) (Pubitemid 46043653)
147. S. Shin, N. Li, N. Kobayashi, J. W. Yoon, H. S. Jun: Remission of diabetes by beta cell regeneration in diabetic mice treated with a recombinant adenovirus expressing betacellulin. Mol Ther (in press), (2008)
148. J. Movassat, B. Portha: Early administration of keratinocyte growth factor improves {beta}-cell regeneration in rat with streptozotocin-induced diabetes. J Endocrinol 195, 333-340 (2007) (Pubitemid 350143113)
149. M. Koizumi, K. Nagai, A. Kida, K. Kami, D. Ito, K. Fujimoto, Y. Kawaguchi, R. Doi: Forced expression of PDX-1 induces insulin production in intestinal epithelia. Surgery 140, 273-280 (2006) (Pubitemid 44176078)
150. S. Nomura, T. Nakamura, T. Hashimoto, Y. Nishio, H. Maegawa, M. Kudo, A. Kashiwagi: MafA differentiates rat intestinal cells into insulin-producing cells. Biochem Biophys Res Commun 349, 136-143 (2006) (Pubitemid 44331773)
151. J. C. Voltarelli, C. E. Couri, A. B. Stracieri, M. C. Oliveira, D. A. Moraes, F. Pieroni, M. Coutinho, K. C. Malmegrim, M. C. Foss-Freitas, B. P. Simoes, M. C. Foss, E. Squiers, R. K. Burt: Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 297, 1568-1576 (2007) (Pubitemid 46588370)