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Therapeutic Potential of Stem Cells in Diabetes

  • Chapter
Stem Cells

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 174))

Abstract

Stem cells possess the ability to self-renew by symmetric divisions and, under certain circumstances, differentiate to a committed lineage by asymmetric cell divisions. Depending on the origin, stem cells are classified as either embryonic or adult. Embryonic stem cells are obtained from the inner cell mass of the blastocyst, a structure that appears during embryonic development at day 6 in humans and day 3.5 in mice. Adult stem cells are present within tissues of adult organisms and are responsible for cell turnover or repopulation of tissues under normal or exceptional circumstances. Taken together, stem cells might represent a potential source of tissues for cell therapy protocols, and diabetes is a candidate disease that may benefit from cell replacement protocols. The pathology of type 1 diabetes is caused by the autoimmune destruction or malfunction of pancreatic β cells, and consequently, a lack of insulin. The absence of insulin is life-threatening, thus requiring diabetic patients to take daily hormone injections from exogenous sources; however, insulin injections do not adequately mimic β cell function. This results in the development of diabetic complications such as neuropathy, nephropathy, retinopathy and diverse cardiovascular disorders. This chapter intends to summarize the possibilities opened by embryonic and adult stem cells in regenerative medicine for the cure of diabetes.

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References

  • 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  CAS  PubMed  Google Scholar 

  • Barshes NR, Lee T, Goodpasture S, Brunicardi FC, Alejandro R, Ricordi C, Soltes G, Barth M, Hamilton D, Goss JA (2004) Achievement of insulin independence via pancreatic islet transplantation using a remote isolation center: a first-year review. Transplant Proc 36:1127–1129

    Article  CAS  PubMed  Google Scholar 

  • Bell GI, Polonsky KS (2001) Diabetes mellitus and genetically programmed defects in β-cell function. Nature 414:788–791

    Article  CAS  PubMed  Google Scholar 

  • Benoist C, Mathis D (1997) Cell death mediators in autoimmune diabetes. No shortage of suspects. Cell 89:1–3

    Article  CAS  PubMed  Google Scholar 

  • Blyszczuk P, Czyz J, Kania G, Wagner M, Roll U, St-Onge L, Wobus A (2003) 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

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Brandhorst H, Brandhorst D, Hess F, Ambrosius D, Brendel M, Kawakami Y, Bretzel RG (2003) Successful human islet isolation utilizing recombinant collagenase. Diabetes 52:1143–1146

    CAS  PubMed  Google Scholar 

  • Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    Article  CAS  PubMed  Google Scholar 

  • Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR (1998) A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2:559–569

    Article  CAS  PubMed  Google Scholar 

  • Chakrabarti SK, Mirmira RG (2003) Transcription factors direct the development and function of pancreatic β cells. Trends Endocrinol Metab 14:78–84

    CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • DeFronzo RA, Ferrannini E, Keen H, Zimmet P (2004) International textbook of diabetes mellitus, 3rd edn. John Wiley, Chichester, UK

    Google Scholar 

  • Dor Y, Brown J, MartÍnez OI, Melton DA (2004) Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46

    Article  CAS  PubMed  Google Scholar 

  • Efrat S (1998) Prospects for gene therapy of insulin-dependent diabetes mellitus. Diabetologia 41:1401–1409

    Article  CAS  PubMed  Google Scholar 

  • Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N, Karasik A (2000) Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 6:568–572

    Article  CAS  PubMed  Google Scholar 

  • Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778

    Article  CAS  PubMed  Google Scholar 

  • Gage FH, Ray J, Fisher LJ (1995) Isolation, characterization, and use of stem cells from CNS. Annu Rev Neurosci 18:159–192

    Article  CAS  PubMed  Google Scholar 

  • Georges P, Muirhead RP, Williams L, Holman S, Tabiin MT, Dean SK, Tuch BE (2002) Comparison of size, viability, and function of fetal pig islet-like cell clusters after digestion using collagenase or liberase. Cell Transplant 11:539–545

    PubMed  Google Scholar 

  • Gray DW, Sudhakaran N, Titus TT, McShane P, Johnson P (2004) Development of a novel digestion chamber for human and porcine islet isolation. Transplant Proc 36:1135–1138

    Article  CAS  PubMed  Google Scholar 

  • Hernández-Sánchez C, Mansilla A, de la Rosa EJ, Pollerberg GE, MartÍnez-Salas E, de Pablo F (2003) Upstream AUGs in embryonic proinsulin mRNA control its low translation level. EMBO J 22:5582–5592

    PubMed  Google Scholar 

  • 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 Biotech 21:763–770

    Article  CAS  Google Scholar 

  • 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 U S A 99:16105–16110

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Jamal A-M, Lipstt M, Hazrati A, Paraskevas S, Agapitos D, Maysinger D, Rosenberg L (2003) Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures. Cell Death Diff 10:987–996

    CAS  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-González XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Lew WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49

    Article  CAS  PubMed  Google Scholar 

  • Kania G, Blyszczuk P, Wobus AM (2004) The generation of insulin-producing cells from embryonic stem cells-a discussion of controversial findings. J Dev Biol 48:1061–1064

    Google Scholar 

  • Kim SK, Hebrok M (2001) Intercellular signals regulating pancreas development and function. Genes Dev 15:111–127

    Article  CAS  PubMed  Google Scholar 

  • Klug MG, Soonpa MH, Koh GY, Field LJ (1996) Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J Clin Invest 98:216–224

    CAS  PubMed  Google Scholar 

  • Kojima H, Fujimiya M, Matsumura K, Younan P, Imaeda, H, Maeda M, Chan L (2003) NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 9:596–603

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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  CAS  PubMed  Google Scholar 

  • Lammert E, Cleaver O, Melton D (2001) Induction of pancreatic differentiation by signals from blood vessels. Science 294:564–567

    Article  CAS  PubMed  Google Scholar 

  • Lechner A, Yang Y-G, Blacken RA, Wang L, Nolan AL, Habener JF (2004) No evidence for significant transdifferentiation of bone marrow into pancreatic β-cells in vivo. Diabetes 53:616–623

    CAS  PubMed  Google Scholar 

  • León-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  Google Scholar 

  • Li M, Pevny L, Lovell-Badge R, Smith A (1998) Generation of purified neural precursors from embryonic stem cells by lineage selection. Curr Biol 8:971–974

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Maechler P, Wollheim CB (2001) Mitochondrial function in normal and diabetic β-cells. Nature 414:807–812

    Article  CAS  PubMed  Google Scholar 

  • Mathis D, Vence L, Benoist C (2001) β-Cell death during progression to diabetes. Nature 414:792–798

    Article  CAS  PubMed  Google Scholar 

  • Melloul D, Marshak S, Cerasi E (2002) Regulation of insulin gene transcription. Diabetologia 45:309–326

    Article  CAS  PubMed  Google Scholar 

  • Milne HM, Burns CJ, Kitsou-Mylona IK, 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  CAS  PubMed  Google Scholar 

  • Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631–642

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki S, Yamato E, Miyazaki J (2004) Regulated expression of Pdx1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. Diabetes 53:1030–1037

    CAS  PubMed  Google Scholar 

  • Moritoh Y, Yamato E, Yasui Y, Miyazaki S, Miyazaki J (2003) Analysis of insulin-producing cells during in vitro differentiation from feeder-free embryonic stem cells. Diabetes 52:1163–1168

    CAS  PubMed  Google Scholar 

  • Müller M, Fleischmann BK, Selbert S, Ji GJ, Endl E, Middeler G, Müller OJ, Schlenke P, Frese S, Wobus AM, Hescheler J, Katus HA, Franz WM (2000) Selection of ventricular-like cardiomyocytes from ES cells in vitro. FASEB J 14:2540–2548

    PubMed  Google Scholar 

  • Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of Oct3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24:372–376

    Article  CAS  PubMed  Google Scholar 

  • Oluwole SF, Oluwole OO, Adeyeri AO, DePaz HA (2004) New strategies in immune tolerance induction. Cell Biochem Biophys Suppl 40:27–48

    PubMed  Google Scholar 

  • Pesce M, Gross MK, Scholer HR (1998) In line with our ancestors: Oct4 and the mammalian germ. Bioessays 20:722–732

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Podolsky DK (1993) Regulation of intestinal epithelial proliferation: a few answers, many questions. Am J Physiol 264:G179–G186

    CAS  PubMed  Google Scholar 

  • Poitout V, Robertson RP (1996) An integrated view of β-cell dysfunction in type 2 diabetes. Annu Rev Med 47:69–83

    CAS  PubMed  Google Scholar 

  • Polak M, Bouchareb-Banaei L, Scharfmann R, Czernichow P (2000) Early pattern of differentiation in the human pancreas. Diabetes 49:225–232

    CAS  PubMed  Google Scholar 

  • Polonsky KS, Sturis J, Bell GI (1996) Non-insulin dependent diabetes mellitus. A genetically programmed failure of the β-cell to compensate for insulin resistance. N Engl J Med 334:777–783

    Article  CAS  PubMed  Google Scholar 

  • Potten CS, Loeffler M (1990) Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110:1001–1020

    CAS  PubMed  Google Scholar 

  • Prentki M, Roduit R, Lameloise N, Corkey BE Assimacopoulos-Jeannet F (2000) Glucotoxicity, lipotoxicity and pancreatic β-cell failure: a role for malonyl-CoA, PPARα and altered lipid partitioning? Can J Diabetes Care 25:36–46

    Google Scholar 

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

    PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Roche E (2003) Type 2 diabetes: gluco-lipo-toxicity and pancreatic β-cell dysfunction. Ars Pharmaceutica 44:313–332

    Google Scholar 

  • Roche E, Sepulcre MP, Enseñat-Waser R, Maestre I, Reig JA, Soria B (2003) Bio-engineering insulin-secreting cells from embryonic stem cells: a review of progress. Med Biol Eng Comp 41:384–391

    CAS  Google Scholar 

  • Ruhnke M, Ungefroren H, Nussler A, Martin F, Brulport M, Schorman W, Hengstler JG, Klapper W, Ulrichs K, Hutchinson JA, Soria B, Parwaresch RM, Heeckt P, Kremer B, Fändrich F (2005) Differentiation of in-vitro modified human peripheral monocytes into hepatocyte-like and pancreatic islet-like cells. Gastroenterology 128:174–1786

    Article  Google Scholar 

  • Ryan EA, Lakey JRT, Paty BW, Imes S, Korbutt GS, Kneteman NM, Bigam D, Rajotte RV, Shapiro AMJ (2002) Successful islet transplantation. Continued insulin reserve provides long-term glycemic control. Diabetes 51:2148–2157

    CAS  PubMed  Google Scholar 

  • Saltiel AR (2001) New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104:517–529

    Article  CAS  PubMed  Google Scholar 

  • Segev H, Fishman B, Ziskind A, Shulman M, Itskovitz-Eldor J (2004) Differentiation of human embryonic stem cells into insulin-producing clusters. Stem Cells 22:265–274

    Article  CAS  PubMed  Google Scholar 

  • Shapiro AMJ, Lakey JRT, 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 corticoid-free immunosuppressive regime. N Eng J Med 343:230–238

    CAS  Google Scholar 

  • Smith AG (1991) Culture and differentiation of embryonic stem cells. J Tissue Culture Methods 13:89–94

    Google Scholar 

  • Smith AG (2001) Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 17:435–462

    Article  CAS  PubMed  Google Scholar 

  • Soria B, Roche E, Berná G, León-Quinto T, Reig JA, Martín F (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49:157–162

    CAS  PubMed  Google Scholar 

  • Soria B, Skoudy A, Martín F (2001) From stem cells to beta cells: new strategies in cell therapy of diabetes mellitus. Diabetologia 44:407–415

    Article  CAS  PubMed  Google Scholar 

  • Tanaka TS, Kunath T, Kimber WL, Jaradat SA, Stagg CA, Usuda M, Yokota T, Niwa H, Rossant J, Ko MS (2002) Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res 12:1921–1928

    Article  CAS  PubMed  Google Scholar 

  • Thorgeirsson SS (1996) Hepatic stem cells in liver regeneration. FASEB J 10:1249–1256

    CAS  PubMed  Google Scholar 

  • Toyooka Y, Tsunekawa N, Takahashi Y, Matsui Y, Satoh M, Noce T (2000) Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech Dev 93:139–149

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Vicario-Abejón C, Yusta-Boyo MJ, Fernández-Moreno C, de Pablo F (2003) Locally born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous insulin-like growth factor-I for differentiation into neurons and glia. J Neurosci 23:895–906

    PubMed  Google Scholar 

  • Wagers AJ, Weissman IL (2004) Plasticity of adult stem cells. Cell 116:639–648

    Article  CAS  PubMed  Google Scholar 

  • Wobus AM, Boheler KR (2005) Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 85:636–678

    Article  Google Scholar 

  • Yang L, Li S, Hatch H, Ahrens K, Cornelius JG, Petersen BE, Peck AB (2002) In vitro transdifferentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci U S A 99:8078–8083

    CAS  PubMed  Google Scholar 

  • Ying Q-L, Stavridis M, Griffiths D, Li M, Smith A (2003) Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 21:183–186

    Article  CAS  PubMed  Google Scholar 

  • Yoo JU, Barthel TS, Nishimura K, Solchaga L, Caplan AI, Goldberg VM, Johnstone B (1998) The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells. J Bone Joint Surg 80:1745–1757

    CAS  PubMed  Google Scholar 

  • Zalzman M, Gupta S, Giri RK, Berkovich I, Sappal BS, Karnieli O, Zern MA, Fleischer N, Efrat S (2003) 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 100:7253–7258

    Article  CAS  PubMed  Google Scholar 

  • Zierath JR, Krook A, Wallberg-Henriksson H (2000) Insulin action and insulin resistance in human skeletal muscle. Diabetologia 43:821–835

    Article  CAS  PubMed  Google Scholar 

  • Zimmet P, Alberti KGMM, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787

    Article  CAS  PubMed  Google Scholar 

  • Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritzs W, Müller 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

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Instituto de Bioingenieria, Universidad Miguel Hernandez, 03550, San Juan, Spain

    E. Roche, R. Enseñat-Waser, J.A. Reig, J. Jones, T. León-Quinto & B. Soria

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  1. E. Roche
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  2. R. Enseñat-Waser
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  3. J.A. Reig
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  4. J. Jones
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  5. T. León-Quinto
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  6. B. Soria
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Editors and Affiliations

  1. In Vitro Differentiation Group, Dept. of Cytogenetics, Leibnitz Institute of Plant Genetics and Crop Plant Research (IPK), Corrensstr. 3, D-06466, Gatersleben, Germany

    Anna M. Wobus PhD

  2. Laboratory of Cardiovascular Science, Gerontology Research Program, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Kenneth R. Boheler PhD (Investigator) (Investigator)

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Roche, E., Enseñat-Waser, R., Reig, J., Jones, J., León-Quinto, T., Soria, B. (2006). Therapeutic Potential of Stem Cells in Diabetes. In: Wobus, A.M., Boheler, K.R. (eds) Stem Cells. Handbook of Experimental Pharmacology, vol 174. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-31265-X_7

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