Umbilical Cord Stem Cells for Pancreatic Regenerative Medicine

  • Hélène Le Roy
  • Nicolas Forraz
  • Marcin Jurga
  • Colin P. McGuckin
Chapter

Abstract

Diabetes mellitus is one of the leading causes of morbidity and mortality in many countries and is considered as one of the epidemics of the twenty-first century. Current diabetes treatment is mostly based around daily insulin injection. Pancreas or islet transplantation first appeared as a good alternative, but lack of donor calls for more reliable clinical approaches. Recently, stem cell-based therapies have emerged as promising alternatives for pancreatic regenerative medicine. This chapter will review recent innovative clinical and preclinical applications used for diabetes treatment ranging from insulin injection to newly established cellular clinical trials with umbilical cord stem cells.

Keywords

Obesity DMSO Polypeptide Hyperglycemia Glucagon 

References

  1. 1.
    Limbert C, et al. Beta-cell replacement and regeneration: strategies of cell-based therapy for type 1 diabetes mellitus. Diabetes Res Clin Pract. 2008;79(3):389–99.PubMedCrossRefGoogle Scholar
  2. 2.
    Sabin MA, Cameron FJ, Werther GA. Type 1 diabetes – still the commonest form of diabetes in children. Aust Fam Physician. 2009;38(9):695–7.PubMedGoogle Scholar
  3. 3.
    Sun B, et al. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. Biochem Biophys Res Commun. 2007;354(4):919–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Montanya E. Islet- and stem-cell-based tissue engineering in diabetes. Curr Opin Biotechnol. 2004;15(5):435–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Wild S, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Mehers KL, Gillespie KM. The genetic basis for type 1 diabetes. Br Med Bull. 2008;88(1):115–29.PubMedCrossRefGoogle Scholar
  7. 7.
    Aribi M. Candidate genes implicated in type 1 diabetes susceptibility. Curr Diabetes Rev. 2008;4(2):110–21.PubMedCrossRefGoogle Scholar
  8. 8.
    MacFarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome. 2009;20(9–10):624–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Zipris D. Epidemiology of type 1 diabetes and what animal models teach us about the role of viruses in ­disease mechanisms. Clin Immunol. 2009;131(1):11–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Chowdhury TA, Mijovic CH, Barnett AH. The aetiology of type I diabetes. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13(2):181–95.PubMedCrossRefGoogle Scholar
  11. 11.
    Kraine MR, Tisch RM. The role of environmental factors in insulin-dependent diabetes mellitus: an unresolved issue. Environ Health Perspect. 1999;107 Suppl 5:777–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Gremizzi C, et al. Impact of pancreas transplantation on type 1 diabetes-related complications. Curr Opin Organ Transplant. 2010;15(1):119–23.PubMedCrossRefGoogle Scholar
  13. 13.
    de La Sierra A, Ruilope LM. Treatment of hypertension in diabetes mellitus. Curr Hypertens Rep. 2000;2(3):335–42.CrossRefGoogle Scholar
  14. 14.
    Barrios V, Escobar C. Diabetes and hypertension. What is new? Minerva Cardioangiol. 2009;57(6):705–22.PubMedGoogle Scholar
  15. 15.
    Retnakaran R, Zinman B. Type 1 diabetes, hyperglycaemia, and the heart. Lancet. 2008;371(9626):1790–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Crawford TN, et al. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009;5(1):8–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Sanchez AP, Sharma K. Transcription factors in the pathogenesis of diabetic nephropathy. Expert Rev Mol Med. 2009;11:e13.PubMedCrossRefGoogle Scholar
  18. 18.
    Harris DT. Non-haematological uses of cord blood stem cells. Br J Haematol. 2009;147(2):177–84.PubMedCrossRefGoogle Scholar
  19. 19.
    Liao YH, Verchere CB, Warnock GL. Adult stem or progenitor cells in treatment for type 1 diabetes: current progress. Can J Surg. 2007;50(2):137–42.PubMedGoogle Scholar
  20. 20.
    Clark PM. Assays for insulin, proinsulin(s) and C-peptide. Ann Clin Biochem. 1999;36(Pt 5):541–64.PubMedGoogle Scholar
  21. 21.
    Kelly WD, et al. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery. 1967;61(6):827–37.PubMedGoogle Scholar
  22. 22.
    Shapira Z, Yussim A, Mor E. Pancreas transplantation. J Pediatr Endocrinol Metab. 1999;12(1):3–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Lacy PE. Pancreatic transplantation as a means of insulin delivery. Diabetes Care. 1982;5 Suppl 1:93–7.PubMedGoogle Scholar
  24. 24.
    Ballinger WF, Lacy PE. Transplantation of intact pancreatic islets in rats. Surgery. 1972;72(2):175–86.PubMedGoogle Scholar
  25. 25.
    Shapiro AM, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Azzi J, et al. Immunological aspects of pancreatic islet cell transplantation. Expert Rev Clin Immunol. 2010;6(1):111–24.PubMedCrossRefGoogle Scholar
  27. 27.
    Close NC, Hering BJ, Eggerman TL. Results from the inaugural year of the Collaborative Islet Transplant Registry. Transplant Proc. 2005;37(2):1305–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Home PD, et al. A comparison of the activity and disposal of semi-synthetic human insulin and porcine insulin in normal man by the glucose clamp technique. Diabetologia. 1982;22(1):41–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Wilson ME, Scheel D, German MS. Gene expression cascades in pancreatic development. Mech Dev. 2003;120(1):65–80.PubMedCrossRefGoogle Scholar
  30. 30.
    Bernardo AS, Hay CW, Docherty K. Pancreatic transcription factors and their role in the birth, life and survival of the pancreatic beta cell. Mol Cell Endocrinol. 2008;294(1–2):1–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Xu X, et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell. 2008;132(2):197–207.PubMedCrossRefGoogle Scholar
  32. 32.
    Zaret KS. Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet. 2008;9(5):329–40.PubMedCrossRefGoogle Scholar
  33. 33.
    Sander M, German MS. The beta cell transcription factors and development of the pancreas. J Mol Med. 1997;75(5):327–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhou Q, et al. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008;455(7213):627–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Suzuki A, Nakauchi H, Taniguchi H. Glucagon-like peptide 1 (1–37) converts intestinal epithelial cells into insulin-producing cells. Proc Natl Acad Sci USA. 2003;100(9):5034–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Narushima M, et al. A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol. 2005;23(10):1274–82.PubMedCrossRefGoogle Scholar
  37. 37.
    Petropavlovskaia M, Rosenberg L. Identification and characterization of small cells in the adult pancreas: potential progenitor cells? Cell Tissue Res. 2002;310(1):51–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Bouwens L. Islet morphogenesis and stem cell markers. Cell Biochem Biophys. 2004;40(3 Suppl):81–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Bouwens L. Transdifferentiation versus stem cell hypothesis for the regeneration of islet beta-cells in the pancreas. Microsc Res Tech. 1998;43(4):332–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Wang RN, Kloppel G, Bouwens L. Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia. 1995;38(12):1405–11.PubMedCrossRefGoogle Scholar
  41. 41.
    Rooman I, Lardon J, Bouwens L. Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue. Diabetes. 2002;51(3):686–90.PubMedCrossRefGoogle Scholar
  42. 42.
    Heremans Y, et al. Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3. J Cell Biol. 2002;159(2):303–12.PubMedCrossRefGoogle Scholar
  43. 43.
    Taniguchi H, et al. beta-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther. 2003;10(1):15–23.PubMedCrossRefGoogle Scholar
  44. 44.
    Zulewski H, et al. Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 2001;50(3):521–33.PubMedCrossRefGoogle Scholar
  45. 45.
    Hall PA, Lemoine NR. Rapid acinar to ductal trans­differentiation in cultured human exocrine pancreas. J Pathol. 1992;166(2):97–103.PubMedCrossRefGoogle Scholar
  46. 46.
    Horb ME, et al. Experimental conversion of liver to pancreas. Curr Biol. 2003;13(2):105–15.PubMedCrossRefGoogle Scholar
  47. 47.
    Ferber S, et al. Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med. 2000;6(5):568–72.PubMedCrossRefGoogle Scholar
  48. 48.
    Yang L, et al. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA. 2002;99(12):8078–83.PubMedCrossRefGoogle Scholar
  49. 49.
    Yoshida S, et al. PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes. 2002;51(8):2505–13.PubMedCrossRefGoogle Scholar
  50. 50.
    Street CN, Rajotte RV, Korbutt GS. Stem cells: a promising source of pancreatic islets for transplantation in type 1 diabetes. Curr Top Dev Biol. 2003;58:111–36.PubMedCrossRefGoogle Scholar
  51. 51.
    Mishra PK, et al. Stem cells as a therapeutic target for diabetes. Front Biosci. 2010;15:461–77.PubMedCrossRefGoogle Scholar
  52. 52.
    Hori Y. Insulin-producing cells derived from stem/progenitor cells: therapeutic implications for diabetes mellitus. Med Mol Morphol. 2009;42(4):195–200.PubMedCrossRefGoogle Scholar
  53. 53.
    Cai J, Weiss ML, Rao MS. In search of “stemness”. Exp Hematol. 2004;32(7):585–98.PubMedCrossRefGoogle Scholar
  54. 54.
    McGuckin C, Forraz N. The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif. 2011;44 Suppl 1:60–9.PubMedGoogle Scholar
  55. 55.
    McGuckin CP, Forraz N. Umbilical cord blood stem cells – an ethical source for regenerative medicine. Med Law. 2008;27(1):147–65.PubMedGoogle Scholar
  56. 56.
    McGuckin CP, Forraz N. Potential for access to embryonic-like cells from human umbilical cord blood. Cell Prolif. 2008;41 Suppl 1:31–40.PubMedGoogle Scholar
  57. 57.
    Kern S, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006;24(5):1294–301.PubMedCrossRefGoogle Scholar
  58. 58.
    Leeb C, et al. Promising new sources for pluripotent stem cells. Stem Cell Rev. 2010;6(1):15–26.PubMedCrossRefGoogle Scholar
  59. 59.
    Zhao Y, Wang H, Mazzone T. Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics. Exp Cell Res. 2006;312(13):2454–64.PubMedCrossRefGoogle Scholar
  60. 60.
    Gao F, et al. Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells. Chin Med J (Engl). 2008;121(9):811–8.Google Scholar
  61. 61.
    Hu YH, et al. A secretory function of human insulin-producing cells in vivo. Hepatobiliary Pancreat Dis Int. 2009;8(3):255–60.PubMedGoogle Scholar
  62. 62.
    Beattie GM, et al. A novel approach to increase human islet cell mass while preserving beta-cell function. Diabetes. 2002;51(12):3435–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Itskovitz-Eldor J, et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med. 2000;6(2):88–95.PubMedGoogle Scholar
  64. 64.
    Lumelsky N, et al. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science. 2001;292(5520):1389–94.PubMedCrossRefGoogle Scholar
  65. 65.
    Jiang W, et al. In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res. 2007;17(4):333–44.PubMedCrossRefGoogle Scholar
  66. 66.
    Jiang Y, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418(6893):41–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Ianus A, et al. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 2003;111(6):843–50.PubMedGoogle Scholar
  68. 68.
    Oh SH, et al. Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest. 2004;84(5):607–17.PubMedCrossRefGoogle Scholar
  69. 69.
    Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol. 2004;10(20):3016–20.PubMedGoogle Scholar
  70. 70.
    Limbert C, Seufert J. In vitro (re)programming of human bone marrow stromal cells toward insulin-producing phenotypes. Pediatr Diabetes. 2009;10(6):413–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Karnieli O, et al. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells. 2007;25(11):2837–44.PubMedCrossRefGoogle Scholar
  72. 72.
    Koblas T, Harman SM, Saudek F. The application of umbilical cord blood cells in the treatment of diabetes mellitus. Rev Diabet Stud. 2005;2(4):228–34.PubMedCrossRefGoogle Scholar
  73. 73.
    McGuckin CP, et al. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif. 2005;38(4):245–55.PubMedCrossRefGoogle Scholar
  74. 74.
    McGuckin C, et al. Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro. Nat Protoc. 2008;3(6):1046–55.PubMedCrossRefGoogle Scholar
  75. 75.
    Haller MJ, et al. Autologous umbilical cord blood infusion for type 1 diabetes. Exp Hematol. 2008;36(6):710–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Haller MJ, et al. Autologous umbilical cord blood transfusion in very young children with type 1 diabetes. Diabetes Care. 2009;32(11):2041–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Hélène Le Roy
    • 1
  • Nicolas Forraz
    • 1
  • Marcin Jurga
    • 1
  • Colin P. McGuckin
    • 1
  1. 1.CTI-LYON, Cell Therapy Research InstituteMeyzieu-LYONFrance

Personalised recommendations