Skip to main content
SpringerLink
Log in

Stem Cells as a Cure for Diabetes

  • Chapter
Pancreatic Beta Cell in Health and Disease

  • 1570 Accesses

Abstract

Clinical islet transplantation trials have shown that it is possible to at least partially restore functional beta-cell mass in type 1 diabetic patients. However, the scarcity of organ donors and need for intensive immunosuppression prevent the widespread use of this treatment regimen. Progress in stem cell biology provides hope for the solution of these problems. New beta cells could be grown in the laboratory from pancreatic precursors or from more multipotent stem cells. Neogenesis of islets from intrapancreatic precursors has been demonstrated in a number of studies. Fully differentiated beta cells have only been derived in primary cultures, mainly reflecting transdifferentiation from acinar or ductal cells. It is unlikely that these cells could provide a quantitatively sufficient source for cell transplantation. However, the stimulation of endogenous beta-cell regeneration is a promising therapeutic possibility. Extensive proliferation of supposed pancreatic tissue stem cells has also been found, but full maturation of the expanded cells into functional islet cells has not been reported. The most promising possibility to generate theoretically unlimited numbers of beta cells is based on the use of embryonic stem (ES) cells. Human ES cells can be taken through a multiphase differentiation protocol to become insulin-expressing cells that phenotypically resemble immature human fetal beta cells. This field is still in its infancy and many problems need to be solved before ES-cell based products could be developed to the level required for clinical trials in diabetes.

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 149.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ricordi C, Strom TB (2004) Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol 4:259–268

    Article  PubMed  CAS  Google Scholar 

  2. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV (2000) Islet transplantation in seven patients With type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen [See Comments]. N Engl J Med 343:230–238

    Article  PubMed  CAS  Google Scholar 

  3. Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355:1318–1330

    Article  PubMed  CAS  Google Scholar 

  4. Chong AS, Shen J, Tao J, Yin D, Kuznetsov A, Hara M, Philipson LH (2006) Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell regeneration. Science 311:1774–1775

    Article  PubMed  CAS  Google Scholar 

  5. Nishio J, Gaglia JL, Turvey SE, Campbell C, Benoist C, Mathis D (2006) Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution. Science 311:1775–1778

    Article  PubMed  CAS  Google Scholar 

  6. Suri A, Calderon B, Esparza TJ, Frederick K, Bittner P, Unanue ER (2006) Immunological reversal of autoimmune diabetes without hematopoietic replacement of beta cells. Science 311:1778–1780

    Article  PubMed  CAS  Google Scholar 

  7. Kodama S, Kuhtreiber W, Fujimura S, Dale EA, Faustman DL (2003) Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 302:1223–1227

    Article  PubMed  CAS  Google Scholar 

  8. 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: 41–46

    Article  PubMed  CAS  Google Scholar 

  9. Tyrberg B, Ustinov J, Otonkoski T, Andersson A (2001) Stimulated endocrine cell proliferation and differentiation in transplanted human pancreatic islets: effects of the ob gene and compensatory growth of the implantation organ. Diabetes 50:301–307

    Article  PubMed  CAS  Google Scholar 

  10. Bouwens L, Lu WG, Dekrijger RR (1997) Proliferation and differentiation in the human fetal endocrine pancreas. Diabetologia 40:398–404

    Article  PubMed  CAS  Google Scholar 

  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 42:1715–1720

    Article  PubMed  CAS  Google Scholar 

  12. Rafaeloff R, Pittenger GL, Barlow SW, Qin XF, Yan B, Rosenberg L, Duguid WP, Vinik AI (1997) Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters. J Clin Invest 99:2100–2109

    Article  PubMed  CAS  Google Scholar 

  13. Gu D, Sarvetnick N (1993) Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice. Development 118:33–46

    PubMed  CAS  Google Scholar 

  14. Rooman I, Lardon J, Bouwens L (2002) Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue. Diabetes 51:686–690

    Article  PubMed  CAS  Google Scholar 

  15. Gepts W (1965) Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14:619–633

    PubMed  CAS  Google Scholar 

  16. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110

    Article  PubMed  CAS  Google Scholar 

  17. Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC (2005) Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia 48:2221–2228

    Article  PubMed  CAS  Google Scholar 

  18. Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O’Neil JJ (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA 97:7999–8004

    Article  PubMed  CAS  Google Scholar 

  19. Petropavlovskaia M, Rosenberg L (2002) Identification and characterization of small cells in the adult pancreas: potential progenitor cells? Cell Tissue Res 310:51–58

    Article  PubMed  Google Scholar 

  20. Gao R, Ustinov J, Pulkkinen MA, Lundin K, Korsgren O, Otonkoski T (2003) Characterization of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes 52:2007–2015

    Article  PubMed  CAS  Google Scholar 

  21. Gao R, Ustinov J, Korsgren O, Otonkoski T (2005) In vitro neogenesis of human islets reflects the plasticity of differentiated human pancreatic cells. Diabetologia 48: 2296–2304

    Article  PubMed  CAS  Google Scholar 

  22. Gao R, Ustinov J, Korsgren O, Mikkola M, Lundin K, Otonkoski T (2006) Maturation of in vitro-generated human islets after transplantation in nude mice. Mol Cell Endocrinol 264:28–34

    Article  PubMed  CAS  Google Scholar 

  23. Banerjee M, Bhonde RR (2003) Islet generation from intra islet precursor cells of diabetic pancreas: in vitro studies depicting in vivo differentiation. JOP 4:137–145

    PubMed  Google Scholar 

  24. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22:1115–1124

    Article  PubMed  CAS  Google Scholar 

  25. Baeyens L, De Breuck S, Lardon J, Mfopou JK, Rooman I, Bouwens L (2005) In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells. Diabetologia 48:49–57

    Article  PubMed  CAS  Google Scholar 

  26. Minami K, Okuno M, Miyawaki K, Okumachi A, Ishizaki K, Oyama K, Kawaguchi M, Ishizuka N, Iwanaga T, Seino S (2005) Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci USA 102:15116–15121

    Article  PubMed  CAS  Google Scholar 

  27. Hao E, Tyrberg B, Itkin-Ansari P, Lakey JR, Geron I, Monosov EZ, Barcova M, Mercola M, Levine F (2006) Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas. Nat Med 12:310–316

    Article  PubMed  CAS  Google Scholar 

  28. Todorov I, Omori K, Pascual M, Rawson J, Nair I, Valiente L, Vuong T, Matsuda T, Orr C, Ferreri K, Smith CV, Kandeel F, Mullen Y (2006) Generation of human islets through expansion and differentiation of non-islet pancreatic cells discarded (pancreatic discard) after islet isolation. Pancreas 32:130–138

    Article  PubMed  Google Scholar 

  29. Sugiyama T, Rodriguez RT, McLean GW, Kim SK (2007) Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS. Proc Natl Acad Sci USA 104:175–180

    Article  PubMed  CAS  Google Scholar 

  30. Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG (2000) Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6:278–282

    Article  PubMed  CAS  Google Scholar 

  31. Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller B, Vallejo M, Thomas MK, Habener JF (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50:521–533

    Article  PubMed  CAS  Google Scholar 

  32. Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM (2004) Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 306:2261–2264

    Article  PubMed  CAS  Google Scholar 

  33. Suzuki A, Nakauchi H, Taniguchi H (2004) Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 53:2143–2152

    Article  PubMed  CAS  Google Scholar 

  34. Lin HT, Chiou SH, Kao CL, Shyr YM, Hsu CJ, Tarng YW, Ho LL, Kwok CF, Ku HH (2006) Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting. World J Gastroenterol 12:4529–4535

    PubMed  Google Scholar 

  35. Ouziel-Yahalom L, Zalzman M, Anker-Kitai L, Knoller S, Bar Y, Glandt M, Herold K, Efrat S (2006) Expansion and redifferentiation of adult human pancreatic islet cells. Biochem Biophys Res Commun 341:291–298

    Article  PubMed  CAS  Google Scholar 

  36. Yamamoto T, Yamato E, Taniguchi H, Shimoda M, Tashiro F, Hosoi M, Sato T, Fujii S, Miyazaki JI (2006) Stimulation of cAMP signalling allows isolation of clonal pancreatic precursor cells from adult mouse pancreas. Diabetologia 49:2359–2367

    Article  PubMed  CAS  Google Scholar 

  37. Piper K, Ball SG, Turnpenny LW, Brickwood S, Wilson DI, Hanley NA (2002) Betacell differentiation during human development does not rely on nestin-positive precursors: implications for stem cell-derived replacement therapy. Diabetologia 45:1045–1047

    Article  PubMed  CAS  Google Scholar 

  38. Selander L, Edlund H (2002) Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev 113:189–192

    Article  PubMed  CAS  Google Scholar 

  39. Treutelaar MK, Skidmore JM, Dias-Leme CL, Hara M, Zhang L, Simeone D, Martin DM, Burant CF (2003) Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet. Diabetes 52:2503–2512

    Article  PubMed  CAS  Google Scholar 

  40. Delacour A, Nepote V, Trumpp A, Herrera PL (2004) Nestin expression in pancreatic exocrine cell lineages. Mech Dev 121:3–14

    Article  PubMed  CAS  Google Scholar 

  41. Oreffo RO, Cooper C, Mason C, Clements M (2005) Mesenchymal stem cells: lineage, plasticity, and skeletal therapeutic potential. Stem Cell Rev 1:169–178

    Article  PubMed  CAS  Google Scholar 

  42. Ianus A, Holz GG, Theise ND, Hussain MA (2003) In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 111:843–850

    PubMed  CAS  Google Scholar 

  43. Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ (2004) In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 53:1721–1732

    Article  PubMed  CAS  Google Scholar 

  44. Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B, Thyssen S, Gray DA, Bhatia M (2003) Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 21:763–770

    Article  PubMed  CAS  Google Scholar 

  45. Choi JB, Uchino H, Azuma K, Iwashita N, Tanaka Y, Mochizuki H, Migita M, Shimada T, Kawamori R, Watada H (2003) Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells. Diabetologia 46:1366–1374

    Article  PubMed  CAS  Google Scholar 

  46. Taneera J, Rosengren A, Renstrom E, Nygren JM, Serup P, Rorsman P, Jacobsen SE (2006) Failure of transplanted bone marrow cells to adopt a pancreatic beta-cell fate. Diabetes 55:290–296

    Article  PubMed  CAS  Google Scholar 

  47. Mathews V, Hanson PT, Ford E, Fujita J, Polonsky KS, Graubert TA (2004) Recruitment of bone marrow-derived endothelial cells to sites of pancreatic beta-cell injury. Diabetes 53:91–98

    Article  PubMed  CAS  Google Scholar 

  48. Yin D, Tao J, Lee DD, Shen J, Hara M, Lopez J, Kuznetsov A, Philipson LH, Chong AS (2006) Recovery of islet beta-cell function in streptozotocin-induced diabetic mice: an indirect role for the spleen. Diabetes 55:3256–3263

    Article  PubMed  CAS  Google Scholar 

  49. Kodama S, Davis M, Faustman DL (2005) Regenerative medicine: a radical reappraisal of the spleen. Trends Mol Med 11:271–276

    Article  PubMed  CAS  Google Scholar 

  50. Faustman DL, Tran SD, Kodama S, Lodde BM, Szalayova I, Key S, Toth ZE, Mezey E (2006) Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice. Science 314:1243; author reply 1243

    Article  PubMed  CAS  Google Scholar 

  51. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  PubMed  CAS  Google Scholar 

  52. Wei CL, Miura T, Robson P, Lim SK, Xu XQ, Lee MY, Gupta S, Stanton L, Luo Y, Schmitt J, Thies S, Wang W, Khrebtukova I, Zhou D, Liu ET, Ruan YJ, Rao M, Lim B (2005) Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells 23:166–185

    Article  PubMed  CAS  Google Scholar 

  53. Pera MF, Trounson AO (2004) Human embryonic stem cells: prospects for development. Development 131:5515–5525

    Article  PubMed  CAS  Google Scholar 

  54. Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N (2000) Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 6:88–95

    PubMed  CAS  Google Scholar 

  55. Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F (2000) insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocininduced diabetic mice. Diabetes 49:157–162

    Article  PubMed  CAS  Google Scholar 

  56. Kahan BW, Jacobson LM, Hullett DA, Ochoada JM, Oberley TD, Lang KM, Odorico JS (2003) Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells: an in vitro model to study islet differentiation. Diabetes 52:2016–2024

    Article  PubMed  CAS  Google Scholar 

  57. Shiroi A, Yoshikawa M, Yokota H, Fukui H, Ishizaka S, Tatsumi K, Takahashi Y (2002) Identification of insulin-producing cells derived from embryonic stem cells by zinc-chelating dithizone. Stem Cells 20:284–292

    Article  PubMed  CAS  Google Scholar 

  58. Leon-Quinto T, Jones J, Skoudy A, Burcin M, Soria B (2004) In vitro directed differentiation of mouse embryonic stem cells into insulin-producing cells. Diabetologia 47:1442–1451

    Article  PubMed  CAS  Google Scholar 

  59. Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M (2001) Insulin production by human embryonic stem cells. Diabetes 50:1691–1697

    Article  PubMed  CAS  Google Scholar 

  60. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394

    Article  PubMed  CAS  Google Scholar 

  61. Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK (2002) Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci USA 99:16105–16110

    Article  PubMed  CAS  Google Scholar 

  62. Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St-Onge L, Wobus AM (2003) 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

    Article  PubMed  CAS  Google Scholar 

  63. Miyazaki S, Yamato E, Miyazaki J (2004) Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. Diabetes 53:1030–1037

    Article  PubMed  CAS  Google Scholar 

  64. Blyszczuk P, Asbrand C, Rozzo A, Kania G, St-Onge L, Rupnik M, Wobus AM (2004) Embryonic stem cells differentiate into insulin-producing cells without selection of nestin-expressing cells. Int J Dev Biol 48:1095–1104

    Article  PubMed  CAS  Google Scholar 

  65. Marenah L, McCluskey JT, Abdel-Wahab YH, O’Harte FP, McClenaghan NH, Flatt PR (2006) A stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing islet-specific genes and hormones. Biol Chem 387:941–947

    Article  PubMed  CAS  Google Scholar 

  66. Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA (2003) Insulin staining of ES cell progeny from insulin uptake. Science 299:363

    PubMed  Google Scholar 

  67. Kania G, Blyszczuk P, Wobus AM (2004) The generation of insulin-producing cells from embryonic stem cells—a discussion of controversial findings. International Journal of Developmental Biology 48:1061–1064

    Article  PubMed  Google Scholar 

  68. Hansson M, Tonning A, Frandsen U, Petri A, Rajagopal J, Englund MC, Heller RS, Hakansson J, Fleckner J, Skold HN, Melton D, Semb H, Serup P (2004) Artifactual insulin release from differentiated embryonic stem cells. Diabetes 53:2603–2609

    Article  PubMed  CAS  Google Scholar 

  69. Roche E, Sepulcre P, Reig JA, Santana A, Soria B (2005) Ectodermal commitment of insulin-producing cells derived from mouse embryonic stem cells. FASEB J 19:1341–1343

    PubMed  CAS  Google Scholar 

  70. Treff NR, Vincent RK, Budde ML, Browning VL, Magliocca JF, Kapur V, Odorico JS (2006) Differentiation of embryonic stem cells conditionally expressing neurogenin 3. Stem Cells 24:2529–2537

    Article  PubMed  CAS  Google Scholar 

  71. Xu X, Kahan B, Forgianni A, Jing P, Jacobson L, Browning V, Treff N, Odorico J (2006) Endoderm and pancreatic islet lineage differentiation from human embryonic stem cells. Cloning Stem Cells 8:96–107

    Article  PubMed  CAS  Google Scholar 

  72. Milne HM, Burns CJ, Kitsou-Mylona I, Luther MJ, Minger SL, Persaud SJ, Jones PM (2005) Generation of insulin-expressing cells from mouse embryonic stem cells. Biochem Biophys Res Commun 328:399–403

    Article  PubMed  CAS  Google Scholar 

  73. Houard N, Rousseau GG, Lemaigre FP (2003) HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells. Diabetologia 46:378–385

    PubMed  CAS  Google Scholar 

  74. Kubo A, Shinozaki K, Shannon JM, Kouskoff V, Kennedy M, Woo S, Fehling HJ, Keller G (2004) Development of definitive endoderm from embryonic stem cells in culture. Development 131:1651–1662

    Article  PubMed  CAS  Google Scholar 

  75. Ku HT, Zhang N, Kubo A, O’Connor R, Mao M, Keller G, Bromberg JS (2004) Committing embryonic stem cells to early endocrine pancreas in vitro. Stem Cells 22:1205–1217

    Article  PubMed  Google Scholar 

  76. Tada S, Era T, Furusawa C, Sakurai H, Nishikawa S, Kinoshita M, Nakao K, Chiba T, Nishikawa S (2005) Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture. Development 132:4363–4374

    Article  PubMed  CAS  Google Scholar 

  77. Halban PA (2004) Cellular sources of new pancreatic beta cells and therapeutic implications for regenerative medicine. Nat Cell Biol 6:1021–1025

    Article  PubMed  CAS  Google Scholar 

  78. Yasunaga M, Tada S, Torikai-Nishikawa S, Nakano Y, Okada M, Jakt LM, Nishikawa S, Chiba T, Era T, Nishikawa S (2005) Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells. Nat Biotechnol 23: 1542–1550

    Article  PubMed  CAS  Google Scholar 

  79. Brolen GK, Heins N, Edsbagge J, Semb H (2005) Signals from the embryonic mouse pancreas induce differentiation of human embryonic stem cells into insulin-producing beta-cell-like cells. Diabetes 54:2867–2874

    Article  PubMed  CAS  Google Scholar 

  80. D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23:1534–1541

    Article  PubMed  CAS  Google Scholar 

  81. Shi Y, Hou L, Tang F, Jiang W, Wang P, Ding M, Deng H (2005) Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid. Stem Cells 23:656–662

    Article  PubMed  CAS  Google Scholar 

  82. Micallef SJ, Janes ME, Knezevic K, Davis RP, Elefanty AG, Stanley EG (2005) Retinoic acid induces Pdx1-positive endoderm in differentiating mouse embryonic stem cells. Diabetes 54:301–305

    Article  PubMed  CAS  Google Scholar 

  83. McLean AB, D’Amour KA, Jones KL, Krishnamoorthy M, Kulik MJ, Reynolds DM, Sheppard AM, Liu H, Xu Y, Baetge EE, Dalton S (2007) Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells 25:29–38

    Article  PubMed  CAS  Google Scholar 

  84. Shiraki N, Lai CJ, Hishikari Y, Kume S (2005) TGF-beta signaling potentiates differentiation of embryonic stem cells to Pdx-1 expressing endodermal cells. Genes Cells 10:503–516

    Article  PubMed  CAS  Google Scholar 

  85. Vaca P, Martin F, Vegara-Meseguer JM, Rovira JM, Berna G, Soria B (2006) Induction of differentiation of embryonic stem cells into insulin-secreting cells by fetal soluble factors. Stem Cells 24:258–265

    Article  PubMed  CAS  Google Scholar 

  86. D’Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE (2006) Production of pancreatic hormoneexpressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24:1392–1401

    Article  PubMed  CAS  Google Scholar 

  87. Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R, Arbel G, Huber I, Satin J, Itskovitz-Eldor J, Gepstein L (2004) Electromechanical integration of cardio myocytes derived from human embryonic stem cells. Nat Biotechnol 22:1282–1289

    Article  PubMed  CAS  Google Scholar 

  88. Martin MJ, Muotri A, Gage F, Varki A (2005) Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med 11:228–232

    Article  PubMed  CAS  Google Scholar 

  89. Heiskanen A, Satomaa T, Tiitinen S, Laitinen A, Mannelin S, Impola U, Mikkola M, Olsson C, Miller-Podraza H, Blomqvist M, Olonen A, Salo H, Lehenkari P, Tuuri T, Otonkoski T, Natunen J, Saarinen J, Laine J (2007) N-glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is substantially reversible. Stem Cells 25:197–202

    Article  PubMed  CAS  Google Scholar 

  90. Ellerstrom C, Strehl R, Moya K, Andersson K, Bergh C, Lundin K, Hyllner J, Semb H (2006) Derivation of a xeno-free human embryonic stem cell line. Stem Cells 24: 2170–2176

    Article  PubMed  Google Scholar 

  91. Allegrucci C, Young LE (2006) Differences between human embryonic stem cell lines. Hum Reprod Update 13:103–120

    Article  PubMed  Google Scholar 

  92. Mikkola M, Olsson C, Palgi J, Ustinov J, Palomaki T, Horelli-Kuitunen N, Knuutila S, Lundin K, Otonkoski T, Tuuri T (2006) Distinct differentiation characteristics of individual human embryonic stem cell lines. BMC Dev Biol 6:40

    Article  PubMed  CAS  Google Scholar 

  93. Roep BO, Stobbe I, Duinkerken G, van Rood JJ, Lernmark A, Keymeulen B, Pipeleers D, Claas FH, de Vries RR (1999) Auto-and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients. Diabetes 48: 484–490

    Article  PubMed  CAS  Google Scholar 

  94. Drukker M, Katchman H, Katz G, Even-Tov Friedman S, Shezen E, Hornstein E, Mandelboim O, Reisner Y, Benvenisty N (2006) Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells. Stem Cells 24:221–229

    Article  PubMed  Google Scholar 

  95. Sasaki H, Hogan BL (1993) Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. Development 118:47–59

    PubMed  CAS  Google Scholar 

  96. Ang SL, Wierda A, Wong D, Stevens KA, Cascio S, Rossant J, Zaret KS (1993) The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development 119:1301–1315

    PubMed  CAS  Google Scholar 

  97. Monaghan AP, Kaestner KH, Grau E, Schutz G (1993) Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. Development 119:567–578

    PubMed  CAS  Google Scholar 

  98. Kanai-Azuma M, Kanai Y, Gad JM, Tajima Y, Taya C, Kurohmaru M, Sanai Y, Yonekawa H, Yazaki K, Tam PP, Hayashi Y (2002) Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 129:2367–2379

    PubMed  CAS  Google Scholar 

  99. Belo JA, Bouwmeester T, Leyns L, Kertesz N, Gallo M, Follettie M, De Robertis EM (1997) Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech Dev 68:45–57

    Article  PubMed  CAS  Google Scholar 

  100. Biben C, Stanley E, Fabri L, Kotecha S, Rhinn M, Drinkwater C, Lah M, Wang CC, Nash A, Hilton D, Ang SL, Mohun T, Harvey RP (1998) Murine cerberus homologue mCer-1: a candidate anterior patterning molecule. Dev Biol 194:135–151

    Article  PubMed  CAS  Google Scholar 

  101. Shawlot W, Deng JM, Behringer RR (1998) Expression of the mouse cerberus-related gene, Cerr1, suggests a role in anterior neural induction and somitogenesis. Proc Natl Acad Sci USA 95:6198–6203

    Article  PubMed  CAS  Google Scholar 

  102. Pearce JJ, Penny G, Rossant J (1999) A mouse cerberus/Dan-related gene family. Dev Biol 209:98–110

    Article  PubMed  CAS  Google Scholar 

  103. McGrath KE, Koniski AD, Maltby KM, McGann JK, Palis J (1999) Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol 213:442–456

    Article  PubMed  CAS  Google Scholar 

  104. Blum M, Gaunt SJ, Cho KW, Steinbeisser H, Blumberg B, Bittner D, De Robertis EM (1992) Gastrulation in the mouse: the role of the homeobox gene goosecoid. Cell 69:1097–1106

    Article  PubMed  CAS  Google Scholar 

  105. Liao WS, Conn AR, Taylor JM (1980) Changes in rat alpha 1-fetoprotein and albumin mRNA levels during fetal and neonatal development. J Biol Chem 255:10036–10039

    PubMed  CAS  Google Scholar 

  106. Muglia L, Locker J (1984) Developmental regulation of albumin and alphafetoprotein gene expression in the rat. Nucleic Acids Res 12:6751–6762

    Article  PubMed  CAS  Google Scholar 

  107. Shook D, Keller R (2003) Mechanisms, mechanics and function of epithelialmesenchymal transitions in early development. Mech Dev 120:1351–1383

    Article  PubMed  CAS  Google Scholar 

  108. Hatta K, Takeichi M (1986) Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320:447–449

    Article  PubMed  CAS  Google Scholar 

  109. Radice GL, Rayburn H, Matsunami H, Knudsen KA, Takeichi M, Hynes RO (1997) Developmental defects in mouse embryos lacking N-cadherin. Dev Biol 181:64–78

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hospital for Children and Adolescents and the Biomedicum Stem Cell Center, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, Haartmaninkatu 8, FI-00014, Helsinki, Finland

    Timo Otonkoski, Meenal Banerjee & Karolina Lundin

Authors
  1. Timo Otonkoski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meenal Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karolina Lundin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Susumu Seino M.D., D.M. Sci. (Professor) (Professor)

  2. Medicine and Human Genetics, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA

    Graeme I. Bell Ph.D. (Louis Block Distinguished Service Professor) (Louis Block Distinguished Service Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer

About this chapter

Cite this chapter

Otonkoski, T., Banerjee, M., Lundin, K. (2008). Stem Cells as a Cure for Diabetes. In: Seino, S., Bell, G.I. (eds) Pancreatic Beta Cell in Health and Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-75452-7_14

Download citation

Publish with us

Policies and ethics

Search

Navigation