Advertisement

Overview of Pancreatic Replacement of β-Cells from Various Cell Sources

  • Subhanwita Sarkar Dey
  • Noriko Yoshida
  • Kouichi Hasegawa
Chapter

Abstract

Deregulation of glucose uptake leads to the metabolic disorder popularly known as diabetes. The islet β-cells are pancreatic endocrine cells that secret insulin, and the loss of these islet cells results in lower production of insulin thereby leading to hyperglycemia. Replenishment of β-cell through in vivo cell production or in vivo cell regeneration is the ongoing trend of islet cell research. Human embryonic stem cells and induced pluripotent stem cells are majorly being induced to produce insulin-producing cells. These approaches seem to be the best candidates for clinical trial. However, drawbacks such as teratoma formation, autoimmunity, and efficiency of glucose-responded insulin production are yet to be addressed. Transdifferentiation using the concept of direct reprogramming has shown another possibility of producing insulin-producing cells. Many ongoing clinical trials are using various cell sources for type I diabetes treatment. Some of the cell therapies for type I diabetes have started incorporating essential genes lacking in diabetic patients. In this context, adult progenitor cells are the least studied ones. The presence of adult pancreatic progenitor cells still remains controversial. To isolate live progenitor cells and understand the capacity of β-cell differentiation in the cells, novel progenitor markers should be identified, isolated, and characterized.

Keywords

Islet Cell Islet Transplantation Human Pancreas Definitive Endoderm Human Pluripotent Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    World Health Organization (WHO) (2013) “Diabetes” Media Centre, Fact Sheet No. 312. http://www.who.int/mediacentre/factsheets/fs312/en/
  2. 2.
    International Diabetes Federation (2013) IDF diabetes atlas, 6th edn. International Diabetes Federation, Brussels. http://www.idf.org/diabetesatlas
  3. 3.
    Yoon J, Jun H (2005) Autoimmune destruction of pancreatic b cells. Am J Ther 591:580–591CrossRefGoogle Scholar
  4. 4.
    Bouwens L, Houbracken I, Mfopou JK (2013) The use of stem cells for pancreatic regeneration in diabetes mellitus. Nat Rev Endocrinol 9:598–606PubMedCrossRefGoogle Scholar
  5. 5.
    Yi P, Park J-S, Melton DA (2013) Betatrophin: a hormone that controls pancreatic β cell proliferation. Cell 153:747–758PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Butler AE et al (2007) Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis. Diabetologia 50:2323–2331PubMedCrossRefGoogle Scholar
  7. 7.
    Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC (2008) Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 10 Suppl 4:32–42PubMedCrossRefGoogle Scholar
  8. 8.
    Rojas A, Khoo A, Tejedo JR, Bedoya FJ, Martín F (2010) Islet cell development. Adv Exp Med Biol 654:59–75PubMedCrossRefGoogle Scholar
  9. 9.
    Naftanel MA, Harlan DM (2004) Pancreatic islet transplantation. PLoS Med 1:e58; quiz e75PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Jacobs-Tulleneers-Thevissen D et al (2010) Human islet cell implants in a nude rat model of diabetes survive better in omentum than in liver with a positive influence of beta cell number and purity. Diabetologia 53:1690–1699PubMedCrossRefGoogle Scholar
  11. 11.
    Shih HP et al (2012) A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation. Development 139:2488–2499PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Kopp JL et al (2011) Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development 138:653–665PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Gu G, Dubauskaite J, Melton DA (2002) Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129:2447–2457PubMedGoogle Scholar
  14. 14.
    Sosa-pineda B (2004) Molecules and the gene Pax4 is an essential regulator of pancreatic β-cell. Development 18:289–294Google Scholar
  15. 15.
    Collombat P et al (2003) Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 17:2591–2603PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Kroon E et al (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26:443–452PubMedCrossRefGoogle Scholar
  17. 17.
    Assady S et al (2001) Insulin production by human embryonic stem cells. Diabetes 50:1691–1697PubMedCrossRefGoogle Scholar
  18. 18.
    Wei R et al (2013) Insulin-producing cells derived from human embryonic stem cells: comparison of definitive endoderm- and nestin-positive progenitor-based differentiation strategies. PLoS One 8:e72513PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Kunisada Y, Tsubooka-Yamazoe N, Shoji M, Hosoya M (2012) Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. Stem Cell Res 8:274–284PubMedCrossRefGoogle Scholar
  20. 20.
    Hosoya M (2012) Preparation of pancreatic β-cells from human iPS cells with small molecules. Islets 4:249–252PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Jiang J et al (2007) Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25:1940–1953PubMedCrossRefGoogle Scholar
  22. 22.
    Wen Y, Chen B, Ildstad ST (2011) Stem cell-based strategies for the treatment of type 1 diabetes mellitus. Expert Opin Biol Ther 11:41–53PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Zhang D et al (2009) Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 19:429–438PubMedCrossRefGoogle Scholar
  24. 24.
    Sui L, Mfopou JK, Chen B, Sermon K, Bouwens L (2013) Transplantation of human embryonic stem cell-derived pancreatic endoderm reveals a site-specific survival, growth, and differentiation. Cell Transplant 22:821–830PubMedCrossRefGoogle Scholar
  25. 25.
    Wu H, Wen D, Mahato RI (2013) Third-party mesenchymal stem cells improved human islet transplantation in a humanized diabetic mouse model. Mol Ther 21:1778–1786PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Xie H et al (2013) Role of injured pancreatic extract promotes bone marrow-derived mesenchymal stem cells efficiently differentiate into insulin-producing cells. PLoS One 8:e76056PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Gershengorn MC et al (2004) Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 306:2261–2264PubMedCrossRefGoogle Scholar
  28. 28.
    Dalvi MP, Umrani MR, Joglekar MV, Hardikar AA (2009) Human pancreatic islet progenitor cells demonstrate phenotypic plasticity in vitro. J Biosci 34:523–528PubMedCrossRefGoogle Scholar
  29. 29.
    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 111:843–850PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Taneera J et al (2006) Failure of transplanted bone marrow cells to adopt a pancreatic beta-cell fate. Diabetes 55:290–296PubMedCrossRefGoogle Scholar
  31. 31.
    Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168PubMedCrossRefGoogle Scholar
  32. 32.
    Ku HT (2008) Minireview: pancreatic progenitor cells–recent studies. Endocrinology 149:4312–4316PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Szabat M et al (2012) Maintenance of β-cell maturity and plasticity in the adult pancreas: developmental biology concepts in adult physiology. Diabetes 61:1365–1371PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Teta M, Rankin MM, Long SY, Stein GM, Kushner JA (2007) Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev Cell 12:817–826PubMedCrossRefGoogle Scholar
  35. 35.
    Solar M et al (2009) Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth. Dev Cell 17:849–860PubMedCrossRefGoogle Scholar
  36. 36.
    Furuyama K et al (2011) Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet 43:34–41PubMedCrossRefGoogle Scholar
  37. 37.
    Kopinke D, Murtaugh LC (2010) Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas. BMC Dev Biol 10:38PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Inada A et al (2008) Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth. Proc Natl Acad Sci U S A 105:19915–19919PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Xu X et al (2008) Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132:197–207PubMedCrossRefGoogle Scholar
  40. 40.
    Thorel F et al (2010) Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464:1149–1154PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46PubMedCrossRefGoogle Scholar
  42. 42.
    Deltour L et al (1993) Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo. Proc Natl Acad Sci 90:527–531PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Szabat M, Luciani DS, Piret JM, Johnson JD (2009) Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus. Endocrinology 150:1627–1635PubMedCrossRefGoogle Scholar
  44. 44.
    Erickson RP, Grimes J, Venta PJ, Tashian RE (1995) Expression of carbonic anhydrase II (CA II) promoter-reporter fusion genes in multiple tissues of transgenic mice does not replicate normal patterns of expression indicating complexity of CA II regulation in vivo. Biochem Genet 33:421–437PubMedCrossRefGoogle Scholar
  45. 45.
    Rovira M et al (2010) Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci U S A 107:75–80PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Cheung TH, Rando TA (2013) Molecular regulation of stem cell quiescence. Nat Rev Mol Cell Biol 14:329–340PubMedCrossRefGoogle Scholar
  47. 47.
    Szabat M, Johnson JD, Piret JM (2010) Reciprocal modulation of adult beta cell maturity by activin A and follistatin. Diabetologia 53:1680–1689PubMedCrossRefGoogle Scholar
  48. 48.
    Dioum EM et al (2011) A small molecule differentiation inducer increases insulin production by pancreatic β cells. Proc Natl Acad Sci U S A 108:20713–20718PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Ninov N, Borius M, Stainier DYR (2012) Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors. Development 139:1557–1567PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Seaberg RM et al (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22:1115–1124PubMedCrossRefGoogle Scholar
  51. 51.
    Nicholas CR, Kriegstein AR (2010) Regenerative medicine: cell reprogramming gets direct. Nature 463:1031–1032PubMedCrossRefGoogle Scholar
  52. 52.
    Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:627–632PubMedCrossRefGoogle Scholar
  53. 53.
    Courtney M et al (2013) The inactivation of Arx in pancreatic α-cells triggers their neogenesis and conversion into functional β-like cells. PLoS Genet 9:e1003934PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Schuit FC (1997) Is GLUT2 required for glucose sensing? Diabetologia 40:104–111PubMedCrossRefGoogle Scholar
  55. 55.
    Johnson D et al (2007) Glucokinase activators: molecular tools for studying the physiology of insulin-secreting cells. Biochem Soc Trans 35:1208–1210PubMedCrossRefGoogle Scholar
  56. 56.
    Zawalich WS, Bonnet-Eymard M, Zawalich KC (1998) Glucose-induced desensitization of the pancreatic beta-cell is species dependent. Am J Physiol 275:E917–E924PubMedGoogle Scholar
  57. 57.
    McDonald TJ et al (1994) Canine, human, and rat plasma insulin responses to galanin administration: species response differences. Am J Physiol 266:E612–E617PubMedGoogle Scholar
  58. 58.
    Ramracheya RD et al (2008) Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res 44:273–279PubMedCrossRefGoogle Scholar
  59. 59.
    Brun T et al (2008) The diabetes-linked transcription factor Pax4 is expressed in human pancreatic islets and is activated by mitogens and GLP-1. Hum Mol Genet 17:478–489PubMedCrossRefGoogle Scholar
  60. 60.
    Potikha T, Kassem S, Haber EP, Ariel I, Glaser B (2005) p57Kip2 (cdkn1c): sequence, splice variants and unique temporal and spatial expression pattern in the rat pancreas. Lab Invest 85:364–375PubMedCrossRefGoogle Scholar
  61. 61.
    Hay CW, Docherty K (2006) Comparative analysis of insulin gene promoters: implications for diabetes research. Diabetes 55:3201–3213PubMedCrossRefGoogle Scholar
  62. 62.
    Piper Hanley K et al (2010) In vitro expression of NGN3 identifies RAB3B as the predominant Ras-associated GTP-binding protein 3 family member in human islets. J Endocrinol 207:151–161PubMedCentralPubMedCrossRefGoogle Scholar
  63. 64.
    Al-Hasani K et al (2013) Adult duct-lining cells can reprogram into β-like cells able to counter repeated cycles of toxin-induced diabetes. Dev Cell 26:86–100PubMedCrossRefGoogle Scholar
  64. 65.
    Banga A, Akinci E, Greder LV, Dutton JR, Slack JM (2012) In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts. Proc Natl Acad Sci U S A 109:15336–15341PubMedCentralPubMedCrossRefGoogle Scholar
  65. 66.
    Stamp LA et al (2012) The GCTM-5 epitope associated with the mucin-like glycoprotein FCGBP marks progenitor cells in tissues of endodermal origin. Stem Cells 30:1999–2009PubMedCentralPubMedCrossRefGoogle Scholar
  66. 67.
    Demeterco C, Beattie GM, Dib SA, Lopez AD, Hayek A (2000) A role for activin A and betacellulin in human fetal pancreatic cell differentiation and growth. J Clin Endocrinol Metab 85:3892–3897PubMedGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Subhanwita Sarkar Dey
    • 1
  • Noriko Yoshida
    • 2
  • Kouichi Hasegawa
    • 1
    • 2
  1. 1.Institute for Stem Cell Biology and Regenerative Medicine (inStem)National Centre for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR)BangaloreIndia
  2. 2.Institute for Integrated Cell-Material Sciences (iCeMS)Kyoto UniversityKyotoJapan

Personalised recommendations