Skip to main content
SpringerLink
Log in

Embryonic Stem Cells and Pancreatic Differentiation

  • Chapter
  • First Online:
Pancreatic Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 664 Accesses

Abstract

Embryonic stem (ES) cells are derived from the early preimplantation blastocyst. These cells are immortal under defined conditions in vitro, and can be indefinitely expanded without loss of pluripotency. Proof-of-concept experiments demonstrate that they have the ability to spontaneously differentiate into insulin-producing cells, even if at a very low frequency. Here we review the most recent progress at defining conditions (chemical, genetic, or otherwise) for the directed differentiation of both mouse and human ES cells into insulin-producing beta cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S. & Jones, J.M. Embryonic stem cell lines derived from human blastocysts. Science. 282, 1145–7 (1998).

    PubMed  CAS  Google Scholar 

  2. Evans, M.J. & Kaufman, M.H. Establishment in culture of pluripotential cells from mouse embryos. Nature. 292, 154–6 (1981).

    PubMed  CAS  Google Scholar 

  3. Martin, G.R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA. 78, 7634–8 (1981).

    PubMed  CAS  Google Scholar 

  4. Cabrera, O., Berman, D.M., Kenyon, N.S., Ricordi, C., Berggren, P.O. & Caicedo, A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci USA. 103, 2334–9 (2006).

    PubMed  CAS  Google Scholar 

  5. Edlund, H. Developmental biology of the pancreas. Diabetes. 50(Suppl 1), S5–9 (2001).

    PubMed  CAS  Google Scholar 

  6. Kumar, M. & Melton, D. Pancreas specification: a budding question. Curr Opin Genet Dev. 13, 401–7 (2003).

    PubMed  CAS  Google Scholar 

  7. Kubo, A., Shinozaki, K., Shannon, J.M., Kouskoff, V., Kennedy, M., Woo, S., Fehling, H.J. & Keller, G. Development of definitive endoderm from embryonic stem cells in culture. Development. 131, 1651–62 (2004).

    PubMed  CAS  Google Scholar 

  8. Edlund, H. Factors controlling pancreatic cell differentiation and function. Diabetologia. 44, 1071–9 (2001).

    PubMed  CAS  Google Scholar 

  9. Blyszczuk, P., Czyz, J., Kania, G., Wagner, M., Roll, U., St-Onge, L. & Wobus, A.M. Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells. Proc Natl Acad Sci USA. 100, 998–1003 (2003).

    PubMed  CAS  Google Scholar 

  10. Hart, A., Papadopoulou, S. & Edlund, H. Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells. Dev Dyn. 228, 185–93 (2003).

    PubMed  CAS  Google Scholar 

  11. Jiang, J., Au, M., Lu, K., Eshpeter, A., Korbutt, G., Fisk, G. & Majumdar, A.S. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells. 25, 1940–53 (2007).

    PubMed  CAS  Google Scholar 

  12. Slack, J.M. Developmental biology of the pancreas. Development. 121, 1569–80 (1995).

    PubMed  CAS  Google Scholar 

  13. D’Amour, K.A., Agulnick, A.D., Eliazer, S., Kelly, O.G., Kroon, E. & Baetge, E.E. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol. 23, 1534–41 (2005).

    PubMed  Google Scholar 

  14. D’Amour, K.A., Bang, A.G., Eliazer, S., Kelly, O.G., Agulnick, A.D., Smart, N.G., Moorman, M.A., Kroon, E., Carpenter, M.K. & Baetge, E.E. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 24(11):1392–401 (2006).

    PubMed  Google Scholar 

  15. Jiang, J., Au, M., Lu, K., Eshpeter, A., Korbutt, G., Fisk, G. & Majumdar, A.S. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells. 25(8), 1940–53 (2007).

    PubMed  CAS  Google Scholar 

  16. Horb, M.E., Shen, C.N., Tosh, D. & Slack, J.M. Experimental conversion of liver to pancreas. Curr Biol. 13, 105–15 (2003).

    PubMed  CAS  Google Scholar 

  17. Lavon, N., Yanuka, O. & Benvenisty, N. The effect of overexpression of Pdx1 and Foxa2 on the differentiation of human embryonic stem cells into pancreatic cells. Stem Cells. 24, 1923–30 (2006).

    PubMed  CAS  Google Scholar 

  18. Baharvand, H., Jafary, H., Massumi, M. & Ashtiani, S.K. Generation of insulin-secreting cells from human embryonic stem cells. Dev Growth Differ. 48, 323–32 (2006).

    Google Scholar 

  19. Liew, C.G., Shah, N.N., Briston, S.J., Shepherd, R.M., Khoo, C.P., Dunne, M.J., Moore, H.D., Cosgrove, K.E. & Andrews, P.W. PAX4 enhances beta-cell differentiation of human embryonic stem cells. PLoS ONE. 3, e1783 (2008).

    PubMed  Google Scholar 

  20. Hanna, J., Wernig, M., Markoulaki, S., Sun, C.W., Meissner, A., Cassady, J.P., Beard, C., Brambrink, T., Wu, L.C., Townes, T.M. & Jaenisch, R. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science. 318, 1920–3 (2007).

    PubMed  CAS  Google Scholar 

  21. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N. & Yamanaka, S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 26(1), 101–6 (2008).

    PubMed  CAS  Google Scholar 

  22. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. & Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131, 861–72 (2007).

    PubMed  CAS  Google Scholar 

  23. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126, 663–76 (2006).

    PubMed  CAS  Google Scholar 

  24. Baum, C., Kustikova, O., Modlich, U., Li, Z. & Fehse, B. Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum Gene Ther. 17, 253–63 (2006).

    PubMed  CAS  Google Scholar 

  25. Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T. & Yamanaka, S. Generation of mouse induced pluripotent stem cells without viral vectors. Science. 322(5903), 949–53 (2008).

    PubMed  CAS  Google Scholar 

  26. Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., Slukvin, II. & Thomson, J.A. Induced pluripotent stem cell lines derived from human somatic cells. Science. 318, 1917–20 (2007).

    PubMed  CAS  Google Scholar 

  27. Roche, E., Sepulcre, P., Reig, J.A., Santana, A. & Soria, B. Ectodermal commitment of insulin-producing cells derived from mouse embryonic stem cells. FASEB J. 19, 1341–3 (2005).

    PubMed  CAS  Google Scholar 

  28. Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J.A. & Martin, F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes. 49, 157–62 (2000).

    PubMed  CAS  Google Scholar 

  29. Kwon, Y.D., Oh, S.K., Kim, H.S., Ku, S.Y., Kim, S.H., Choi, Y.M. & Moon, S.Y. Cellular manipulation of human embryonic stem cells by TAT-PDX1 protein transduction. Mol Ther. 12, 28–32 (2005).

    PubMed  CAS  Google Scholar 

  30. Rehman, K.K., Bertera, S., Bottino, R., Balamurugan, A.N., Mai, J.C., Mi, Z., Trucco, M. & Robbins, P.D. Protection of islets by in situ peptide-mediated transduction of the Ikappa B kinase inhibitor Nemo-binding domain peptide. J Biol Chem. 278, 9862–8 (2003).

    PubMed  CAS  Google Scholar 

  31. Bosnali, M. & Edenhofer, F. Generation of transducible versions of transcription factors Oct4 and Sox2. Biol Chem. 389, 851–61 (2008).

    PubMed  CAS  Google Scholar 

  32. Edlund, H. Pancreas: how to get there from the gut? Curr Opin Cell Biol. 11, 663–8 (1999).

    PubMed  CAS  Google Scholar 

  33. Kroon, E., Martinson, L.A., Kadoya, K., Bang, A.G., Kelly, O.G., Eliazer, S., Young, H., Richardson, M., Smart, N.G., Cunningham, J., Agulnick, A.D., D’Amour, K.A., Carpenter, M.K. & Baetge, E.E. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 26, 443–52 (2008).

    PubMed  CAS  Google Scholar 

  34. Cowan, C.A., Klimanskaya, I., McMahon, J., Atienza, J., Witmyer, J., Zucker, J.P., Wang, S., Morton, C.C., McMahon, A.P., Powers, D. & Melton, D.A. Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med. 350, 1353–6 (2004).

    PubMed  CAS  Google Scholar 

  35. Bhattacharya, B., Miura, T., Brandenberger, R., Mejido, J., Luo, Y., Yang, A.X., Joshi, B.H., Ginis, I., Thies, R.S., Amit, M., Lyons, I., Condie, B.G., Itskovitz-Eldor, J., Rao, M.S. & Puri, R.K. Gene expression in human embryonic stem cell lines: unique molecular signature. Blood. 103, 2956–64 (2004).

    PubMed  CAS  Google Scholar 

  36. Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S., Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G., Gifford, D.K., Melton, D.A., Jaenisch, R. & Young, R.A. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 122, 947–56 (2005).

    PubMed  CAS  Google Scholar 

  37. Okita, K., Ichisaka, T. & Yamanaka, S. Generation of germline-competent induced pluripotent stem cells. Nature. 448, 313–7 (2007).

    PubMed  CAS  Google Scholar 

  38. Amit, M., Carpenter, M.K., Inokuma, M.S., Chiu, C.P., Harris, C.P., Waknitz, M.A., Itskovitz-Eldor, J. & Thomson, J.A. Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev Biol. 227, 271–8 (2000).

    PubMed  CAS  Google Scholar 

  39. Thomson, J.A. Recent Progress in human embryonic stem cell culture. in Molecular Regulation of Stem Cells Vol. 1, 24 (012) (Keystone Symposia, Banff (Canada), 2005).

    Google Scholar 

  40. Capecchi, M.R. Altering the genome by homologous recombination. Science. 244, 1288–92 (1989).

    PubMed  CAS  Google Scholar 

  41. Ashworth, D., Bishop, M., Campbell, K., Colman, A., Kind, A., Schnieke, A., Blott, S., Griffin, H., Haley, C., McWhir, J. & Wilmut, I. DNA microsatellite analysis of Dolly. Nature. 394, 329 (1998).

    PubMed  CAS  Google Scholar 

  42. Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J. & Campbell, K.H. Viable offspring derived from fetal and adult mammalian cells. Nature. 385, 810–3 (1997).

    PubMed  CAS  Google Scholar 

  43. Lovell-Badge, R.H., Bygrave, A.E., Bradley, A., Robertson, E., Evans, M.J. & Cheah, K.S. Transformation of embryonic stem cells with the human type-II collagen gene and its expression in chimeric mice. Cold Spring Harb Symp Quant Biol. 50, 707–11 (1985).

    PubMed  CAS  Google Scholar 

  44. Thomson, J.A. & Marshall, V.S. Primate embryonic stem cells. Curr Top Dev Biol. 38, 133–65 (1998).

    PubMed  CAS  Google Scholar 

  45. Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R. & McKay, R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science. 292, 1389–94 (2001).

    PubMed  CAS  Google Scholar 

  46. Pearse, A.G. Islet cell precursors are neurones. Nature. 295, 96–7 (1982).

    PubMed  CAS  Google Scholar 

  47. Karsten, S.L., Kudo, L.C., Jackson, R., Sabatti, C., Kornblum, H.I. & Geschwind, D.H. Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks. Dev Biol. 261, 165–82 (2003).

    PubMed  CAS  Google Scholar 

  48. Gu, G., Wells, J.M., Dombkowski, D., Preffer, F., Aronow, B. & Melton, D.A. Global expression analysis of gene regulatory pathways during endocrine pancreatic development. Development. 131, 165–79 (2004).

    PubMed  CAS  Google Scholar 

  49. Zulewski, H., Abraham, E.J., Gerlach, M.J., Daniel, P.B., Moritz, W., Muller, B., Vallejo, M., Thomas, M.K. & Habener, J.F. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 50, 521–33 (2001).

    PubMed  CAS  Google Scholar 

  50. Pictet, R.L., Rall, L.B., Phelps, P. & Rutter, W.J. The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells. Science. 191, 191–2 (1976).

    PubMed  CAS  Google Scholar 

  51. Fontaine, J. & Le Douarin, N.M. Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD series. J Embryol Exp Morphol. 41, 209–22 (1977).

    PubMed  CAS  Google Scholar 

  52. Fontaine, J., Le Lievre, C. & Le Douarin, N.M. What is the developmental fate of the neural crest cells which migrate into the pancreas in the avian embryo? Gen Comp Endocrinol. 33, 394–404 (1977).

    PubMed  CAS  Google Scholar 

  53. Selander, L. & Edlund, H. Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev. 113, 189–92 (2002).

    PubMed  CAS  Google Scholar 

  54. Aiba, K., Sharov, A.A., Carter, M.G., Foroni, C., Vescovi, A.L. & Ko, M.S. Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells. Stem Cells. 24(4), 889–95 (2006).

    PubMed  CAS  Google Scholar 

  55. Fujikawa, T., Oh, S.H., Pi, L., Hatch, H.M., Shupe, T. & Petersen, B.E. Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol. 166, 1781–91 (2005).

    PubMed  CAS  Google Scholar 

  56. Kania, G., Blyszczuk, P., Czyz, J., Navarrete-Santos, A. & Wobus, A.M. Differentiation of mouse embryonic stem cells into pancreatic and hepatic cells. Methods Enzymol. 365, 287–303 (2003).

    PubMed  CAS  Google Scholar 

  57. Hori, Y., Rulifson, I.C., Tsai, B.C., Heit, J.J., Cahoy, J.D. & Kim, S.K. Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci USA. 99, 16105–10 (2002).

    PubMed  CAS  Google Scholar 

  58. Kim, D., Gu, Y., Ishii, M., Fujimiya, M., Qi, M., Nakamura, N., Yoshikawa, T., Sumi, S. & Inoue, K. In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell. Pancreas. 27, e34–41 (2003).

    PubMed  Google Scholar 

  59. Rajagopal, J., Anderson, W.J., Kume, S., Martinez, O.I. & Melton, D.A. Insulin staining of ES cell progeny from insulin uptake. Science. 299, 363 (2003).

    PubMed  Google Scholar 

  60. Sipione, S., Eshpeter, A., Lyon, J.G., Korbutt, G.S. & Bleackley, R.C. Insulin expressing cells from differentiated embryonic stem cells are not beta cells. Diabetologia. 47, 499–508 (2004).

    PubMed  CAS  Google Scholar 

  61. Hansson, M., Tonning, A., Frandsen, U., Petri, A., Rajagopal, J., Englund, M.C., Heller, R.S., Hakansson, J., Fleckner, J., Skold, H.N., Melton, D., Semb, H. & Serup, P. Artifactual insulin release from differentiated embryonic stem cells. Diabetes. 53, 2603–9 (2004).

    PubMed  CAS  Google Scholar 

  62. Alpert, S., Hanahan, D. & Teitelman, G. Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell. 53, 295–308 (1988).

    PubMed  CAS  Google Scholar 

  63. Pugliese, A., Zeller, M., Fernandez, A., Jr., Zalcberg, L.J., Bartlett, R.J., Ricordi, C., Pietropaolo, M., Eisenbarth, G.S., Bennett, S.T. & Patel, D.D. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet. 15, 293–7 (1997).

    PubMed  CAS  Google Scholar 

  64. Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K.L. & Tzukerman, M. Insulin production by human embryonic stem cells. Diabetes. 50, 1691–7 (2001).

    PubMed  CAS  Google Scholar 

  65. Brolen, G.K., Heins, N., Edsbagge, J. & Semb, H. Signals from the embryonic mouse pancreas induce differentiation of human embryonic stem cells into insulin-producing beta-cell-like cells. Diabetes. 54, 2867–74 (2005).

    PubMed  CAS  Google Scholar 

  66. Vaca, P., Martin, F., Vegara-Meseguer, J.M., Rovira, J.M., Berna, G. & Soria, B. Induction of differentiation of embryonic stem cells into insulin-secreting cells by fetal soluble factors. Stem Cells. 24, 258–65 (2006).

    PubMed  CAS  Google Scholar 

  67. Ying, Q.L., Nichols, J., Chambers, I. & Smith, A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell. 115, 281–92 (2003).

    PubMed  CAS  Google Scholar 

  68. Xu, R.H., Peck, R.M., Li, D.S., Feng, X., Ludwig, T. & Thomson, J.A. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods. 2, 185–90 (2005).

    PubMed  CAS  Google Scholar 

  69. Kumar, M., Jordan, N., Melton, D. & Grapin-Botton, A. Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Dev Biol. 259, 109–22 (2003).

    PubMed  CAS  Google Scholar 

  70. Chen, Y., Pan, F.C., Brandes, N., Afelik, S., Solter, M. & Pieler, T. Retinoic acid signaling is essential for pancreas development and promotes endocrine at the expense of exocrine cell differentiation in Xenopus. Dev Biol. 271, 144–60 (2004).

    PubMed  CAS  Google Scholar 

  71. Heit, J.J. & Kim, S.K. Embryonic stem cells and islet replacement in diabetes mellitus. Pediatr Diabetes. 5(Suppl 2), 5–15 (2004).

    PubMed  Google Scholar 

  72. Gao, R., Ustinov, J., Pulkkinen, M.A., Lundin, K., Korsgren, O. & Otonkoski, T. Characterization of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes. 52, 2007–15 (2003).

    PubMed  CAS  Google Scholar 

  73. Lukowiak, B., Vandewalle, B., Riachy, R., Kerr-Conte, J., Gmyr, V., Belaich, S., Lefebvre, J. & Pattou, F. Identification and purification of functional human beta-cells by a new specific zinc-fluorescent probe. J Histochem Cytochem. 49, 519–28 (2001).

    PubMed  CAS  Google Scholar 

  74. Noguchi, H., Kaneto, H., Weir, G.C. & Bonner-Weir, S. PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells. Diabetes. 52, 1732–7 (2003).

    PubMed  CAS  Google Scholar 

  75. Noguchi, H., Matsushita, M., Matsumoto, S., Lu, Y.F., Matsui, H. & Bonner-Weir, S. Mechanism of PDX-1 protein transduction. Biochem Biophys Res Commun. 332, 68–74 (2005).

    PubMed  CAS  Google Scholar 

  76. Dutta, S., Gannon, M., Peers, B., Wright, C., Bonner-Weir, S. & Montminy, M. PDX:PBX complexes are required for normal proliferation of pancreatic cells during development. Proc Natl Acad Sci USA. 98, 1065–70 (2001).

    PubMed  CAS  Google Scholar 

  77. Shen, C.N., Slack, J.M. & Tosh, D. Molecular basis of transdifferentiation of pancreas to liver. Nat Cell Biol. 2, 879–87 (2000).

    PubMed  CAS  Google Scholar 

  78. Cuvelier Delisle, J., Martignat, L., Dubreil, L., Sai, P., Bach, J.M., Louzier, V. & Bosch, S. Pdx-1 or Pdx-1-VP16 protein transduction induces beta-cell gene expression in liver-stem WB cells. BMC Res Notes. 2, 3 (2009).

    Google Scholar 

  79. Munsie, M.J., Michalska, A.E., O’Brien, C.M., Trounson, A.O., Pera, M.F. & Mountford, P.S. Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol. 10, 989–92 (2000).

    PubMed  CAS  Google Scholar 

  80. Byrne, J.A., Pedersen, D.A., Clepper, L.L., Nelson, M., Sanger, W.G., Gokhale, S., Wolf, D.P. & Mitalipov, S.M. Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature. 450, 497–502 (2007).

    PubMed  CAS  Google Scholar 

  81. Hwang, W.S., Lee, B.C., Lee, C.K. & Kang, S.K. Cloned human embryonic stem cells for tissue repair and transplantation. Stem Cell Rev. 1, 99–109 (2005).

    PubMed  CAS  Google Scholar 

  82. Hwang, W.S., Ryu, Y.J., Park, J.H., Park, E.S., Lee, E.G., Koo, J.M., Jeon, H.Y., Lee, B.C., Kang, S.K., Kim, S.J., Ahn, C., Hwang, J.H., Park, K.Y., Cibelli, J.B. & Moon, S.Y. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science. 303, 1669–74 (2004).

    PubMed  CAS  Google Scholar 

  83. Kennedy, D. Editorial retraction. Science. 311, 335 (2006).

    PubMed  CAS  Google Scholar 

  84. French, A.J., Adams, C.A., Anderson, L.S., Kitchen, J.R., Hughes, M.R. & Wood, S.H. Development of human cloned blastocysts following somatic cell nuclear transfer (SCNT) with adult fibroblasts. Stem Cells. 26(2), 485–93 (2008).

    PubMed  CAS  Google Scholar 

  85. Collas, P. Nuclear reprogramming in cell-free extracts. Philos Trans R Soc Lond B Biol Sci. 358, 1389–95 (2003).

    PubMed  CAS  Google Scholar 

  86. Collas, P., Taranger, C.K., Boquest, A.C., Noer, A. & Dahl, J.A. On the way to reprogramming cells to pluripotency using cell-free extracts. Reprod Biomed Online. 12, 762–70 (2006).

    PubMed  CAS  Google Scholar 

  87. Cowan, C.A., Atienza, J., Melton, D.A. & Eggan, K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science. 309, 1369–73 (2005).

    PubMed  CAS  Google Scholar 

  88. Sullivan, S., Pells, S., Hooper, M., Gallagher, E. & McWhir, J. Nuclear reprogramming of somatic cells by embryonic stem cells is affected by cell cycle stage. Cloning Stem Cells. 8, 174–88 (2006).

    PubMed  CAS  Google Scholar 

  89. Park, I.H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M.W., Cowan, C., Hochedlinger, K. & Daley, G.Q. Disease-specific induced pluripotent stem cells. Cell. 134, 877–86 (2008).

    PubMed  CAS  Google Scholar 

  90. Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., Wichterle, H., Henderson, C.E. & Eggan, K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 321, 1218–21 (2008).

    PubMed  CAS  Google Scholar 

  91. Mauritz, C., Schwanke, K., Reppel, M., Neef, S., Katsirntaki, K., Maier, L.S., Nguemo, F., Menke, S., Haustein, M., Hescheler, J., Hasenfuss, G. & Martin, U. Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation. 118, 507–17 (2008).

    PubMed  Google Scholar 

  92. Odorico, J.S., Kaufman, D.S. & Thomson, J.A. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 19, 193–204 (2001).

    PubMed  CAS  Google Scholar 

  93. Vogel, G. Cell biology. Ready or not? Human ES cells head toward the clinic. Science. 308, 1534–8 (2005).

    PubMed  CAS  Google Scholar 

  94. Tamada, K., Wang, X.P. & Brunicardi, F.C. Molecular targeting of pancreatic disorders. World J Surg. 29, 325–33 (2005).

    PubMed  Google Scholar 

  95. Fareed, M.U. & Moolten, F.L. Suicide gene transduction sensitizes murine embryonic and human mesenchymal stem cells to ablation on demand - a fail-safe protection against cellular misbehavior. Gene Ther. 9, 955–62 (2002).

    PubMed  CAS  Google Scholar 

  96. Rosler, E.S., Fisk, G.J., Ares, X., Irving, J., Miura, T., Rao, M.S. & Carpenter, M.K. Long-term culture of human embryonic stem cells in feeder-free conditions. Dev Dyn. 229, 259–74 (2004).

    PubMed  CAS  Google Scholar 

  97. Carpenter, M.K., Rosler, E. & Rao, M.S. Characterization and differentiation of human embryonic stem cells. Cloning Stem Cells. 5, 79–88 (2003).

    PubMed  CAS  Google Scholar 

  98. Baker, D.E., Harrison, N.J., Maltby, E., Smith, K., Moore, H.D., Shaw, P.J., Heath, P.R., Holden, H. & Andrews, P.W. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol. 25, 207–15 (2007).

    PubMed  CAS  Google Scholar 

  99. Imreh, M.P., Gertow, K., Cedervall, J., Unger, C., Holmberg, K., Szoke, K., Csoregh, L., Fried, G., Dilber, S., Blennow, E. & Ahrlund-Richter, L. In vitro culture conditions favoring selection of chromosomal abnormalities in human ES cells. J Cell Biochem. 99, 508–16 (2006).

    PubMed  CAS  Google Scholar 

  100. Adewumi, O., Aflatoonian, B., Ahrlund-Richter, L., Amit, M., Andrews, P.W., Beighton, G., Bello, P.A., Benvenisty, N., Berry, L.S., Bevan, S., Blum, B., Brooking, J., Chen, K.G., Choo, A.B., Churchill, G.A., Corbel, M., Damjanov, I., Draper, J.S., Dvorak, P., Emanuelsson, K., Fleck, R.A., Ford, A., Gertow, K., Gertsenstein, M., Gokhale, P.J., Hamilton, R.S., Hampl, A., Healy, L.E., Hovatta, O., Hyllner, J., Imreh, M.P., Itskovitz-Eldor, J., Jackson, J., Johnson, J.L., Jones, M., Kee, K., King, B.L., Knowles, B.B., Lako, M., Lebrin, F., Mallon, B.S., Manning, D., Mayshar, Y., McKay, R.D., Michalska, A.E., Mikkola, M., Mileikovsky, M., Minger, S.L., Moore, H.D., Mummery, C.L., Nagy, A., Nakatsuji, N., O’Brien, C.M., Oh, S.K., Olsson, C., Otonkoski, T., Park, K.Y., Passier, R., Patel, H., Patel, M., Pedersen, R., Pera, M.F., Piekarczyk, M.S., Pera, R.A., Reubinoff, B.E., Robins, A.J., Rossant, J., Rugg-Gunn, P., Schulz, T.C., Semb, H., Sherrer, E.S., Siemen, H., Stacey, G.N., Stojkovic, M., Suemori, H., Szatkiewicz, J., Turetsky, T., Tuuri, T., van den Brink, S., Vintersten, K., Vuoristo, S., Ward, D., Weaver, T.A., Young, L.A. & Zhang, W. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol. 25, 803–16 (2007).

    PubMed  CAS  Google Scholar 

  101. Osafune, K., Caron, L., Borowiak, M., Martinez, R.J., Fitz-Gerald, C.S., Sato, Y., Cowan, C.A., Chien, K.R. & Melton, D.A. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol. 26, 313–5 (2008).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Development & Stem Cell Laboratory, Diabetes Research Institute University of Miami, Miami, FL, 33136, USA

    Juan Domínguez-Bendala MSc, PhD (Research Assistant Professor of Surgery Pancreatic)

Authors
  1. Juan Domínguez-Bendala MSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan Domínguez-Bendala MSc, PhD .

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Domínguez-Bendala, J. (2009). Embryonic Stem Cells and Pancreatic Differentiation. In: Pancreatic Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60761-132-5_5

Download citation

Publish with us

Policies and ethics

Search

Navigation