Skip to main content
SpringerLink
Log in

Beta Cell Therapies for Type 1 Diabetes

  • Chapter
  • First Online:
Pancreatic Islet Biology

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

Abstract

This chapter intends to introduce the reader to current approaches to targeted treatment for type 1 diabetes (T1D) with the current gold standard clinical therapies that are now offered. In particular, it reviews the most successful transplant techniques for patients with type 1 diabetes and secondary complications. It also provides an in-depth insight into the new frontiers in β-islet cell replacement showing the newest and most novel ways in which scientists and clinicians are now targeting the development of insulin-producing cells in the laboratory, which remains a major focus to finding a cure for type 1 diabetes. This chapter focuses specifically on the newest genetic engineering methods to prevent the onset of diabetes at various stages by a number of techniques to provide numerous ways to produce surrogate β-cells to replace a patient’s own destroyed islet cells. These technologies discussed also include genetic manipulation of the patient’s own cells to produce insulin or ways and techniques to substitute them with the latest types of β-islet cell replacement. These arise in the form of xeno-islet cell transplants and the novel ways by which to prevent their rejection. This ultimately has the ability to achieve the Holy Grail of permanently curing a patient of their type 1 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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
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

  • Akima S et al (2006) Differences in the responses to recombinant human activated protein C against allogeneic and xenogeneic IBMIR. Transplantation 82(1):992

    Google Scholar 

  • Akima S et al (2009) Tirofiban and activated protein C synergistically inhibit the instant blood mediated inflammatory reaction (IBMIR) from allogeneic islet cells exposure to human blood. Am J Transplant 9(7):1533–1540

    Article  CAS  PubMed  Google Scholar 

  • Allen RD et al (1997) Diabetic neuropathy after pancreas transplantation: determinants of recovery. Transplantation 63(6):830–838

    Article  CAS  PubMed  Google Scholar 

  • Allen RD et al (2001) Pancreas and islet transplantation: an unfinished journey. Transplant Proc 33(7–8):3485–3488

    Article  CAS  PubMed  Google Scholar 

  • Anazawa T et al (2010) Improved method of porcine pancreas procurement with arterial flush and ductal injection enhances islet isolation outcome. Transplant Proc 42(6):2032–2035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ansari MJ et al (2003) The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 198(1):63–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babizhayev MA et al (2013) Diabetes mellitus: novel insights, analysis and interpretation of pathophysiology and complications management with imidazole-containing peptidomimetic antioxidants. Recent Pat Drug Deliv Formul 7(3):216–256

    Article  CAS  PubMed  Google Scholar 

  • Balamurugan AN et al (2014) Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999–2010. Am J Transplant 14(11):2595–2606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banting FG et al (1922) Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 12(3):141–146

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barbu AR et al (2006) A perfusion protocol for highly efficient transduction of intact pancreatic islets of Langerhans. Diabetologia 49(10):2388–2391

    Article  CAS  PubMed  Google Scholar 

  • Becker TC et al (1994) Overexpression of hexokinase I in isolated islets of Langerhans via recombinant adenovirus. Enhancement of glucose metabolism and insulin secretion at basal but not stimulatory glucose levels. J Biol Chem 269(33):21234–21238

    CAS  PubMed  Google Scholar 

  • Bennet W et al (2000a) Damage to porcine islets of Langerhans after exposure to human blood in vitro, or after intraportal transplantation to cynomologus monkeys: protective effects of sCR1 and heparin. Transplantation 69(5):711–719

    Article  CAS  PubMed  Google Scholar 

  • Bennet W et al (2000b) Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Ups J Med Sci 105(2):125–133

    Article  CAS  PubMed  Google Scholar 

  • Bergenstal RM et al (2010) Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med 363(4):311–320

    Article  CAS  PubMed  Google Scholar 

  • Bobisse S, Zanovello P, Rosato A (2007) T-cell receptor gene transfer by lentiviral vectors in adoptive cell therapy. Expert Opin Biol Ther 7(6):893–906

    Article  CAS  PubMed  Google Scholar 

  • Boitard C (2012) Pancreatic islet autoimmunity. Presse Med 41(12 p 2):e636–e650

    Google Scholar 

  • Brady JL et al (2013) Anti-CD2 producing pig xenografts effect localized depletion of human T cells in a huSCID model. Xenotransplantation 20(2):100–109

    Article  PubMed  Google Scholar 

  • Bregenholt S et al (2003) The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes. Scand J Immunol 57(5):432–438

    Article  CAS  PubMed  Google Scholar 

  • Bruni A et al (2014) Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges. Diabetes Metab Syndr Obes 7:211–223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Callewaert H et al (2007) Cell loss during pseudoislet formation hampers profound improvements in islet lentiviral transduction efficacy for transplantation purposes. Cell Transplant 16(5):527–537

    Article  CAS  PubMed  Google Scholar 

  • Cardona K et al (2006) Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med 12(3):304–306

    Article  CAS  PubMed  Google Scholar 

  • Carrington EM et al (2010) BH3 mimetics antagonizing restricted prosurvival Bcl-2 proteins represent another class of selective immune modulatory drugs. Proc Natl Acad Sci USA 107(24):10967–10971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chow VC et al (1999) Diabetic retinopathy after combined kidney-pancreas transplantation. Clin Transplant 13(4):356–362

    Article  CAS  PubMed  Google Scholar 

  • Cole CN, Crawford LV, Berg P (1979) Simian virus 40 mutants with deletions at the 3’ end of the early region are defective in adenovirus helper function. J Virol 30(3):683–691

    CAS  PubMed  PubMed Central  Google Scholar 

  • Contreras JL et al (2002) Cytoprotection of pancreatic islets before and early after transplantation using gene therapy. Kidney Int 61(1 Suppl):S79–S84

    Article  PubMed  Google Scholar 

  • Cooper DK et al (2014) Progress in pig-to-non-human primate transplantation models (1998-2013): a comprehensive review of the literature. Xenotransplantation 21(5):397–419

    Article  PubMed  PubMed Central  Google Scholar 

  • Couri CE et al (2009) C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 301(15):1573–1579

    Article  CAS  PubMed  Google Scholar 

  • Cowan PJ, Cooper DK, d’Apice AJ (2014) Kidney xenotransplantation. Kidney Int 85(2):265–275

    Article  PubMed  Google Scholar 

  • Coyle ME, Francis K, Chapman Y (2013) Self-management activities in diabetes care: a systematic review. Aust Health Rev 37(4):513–522

    Article  PubMed  Google Scholar 

  • Creusot RJ et al (2008) Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice. Clin Immunol 127(2):176–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Csete ME et al (1995) Efficient gene transfer to pancreatic islets mediated by adenoviral vectors. Transplantation 59(2):263–268

    Article  CAS  PubMed  Google Scholar 

  • Cullen KS et al (2014) Glucagon induces translocation of glucokinase from the cytoplasm to the nucleus of hepatocytes by transfer between 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase-2 and the glucokinase regulatory protein. Biochim Biophys Acta 1843(6):1123–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denes B et al (2006) Suppression of hyperglycemia in NOD mice after inoculation with recombinant vaccinia viruses. Mol Biotechnol 34(3):317–327

    Article  CAS  PubMed  Google Scholar 

  • Dirice E et al (2009) Adenovirus-mediated TRAIL gene (Ad5hTRAIL) delivery into pancreatic islets prolongs normoglycemia in streptozotocin-induced diabetic rats. Hum Gene Ther 20(10):1177–1189

    Article  CAS  PubMed  Google Scholar 

  • du Toit DF et al (1998) Immunosuppression with cyclosporin A in combination with mycophenolate mofetil suppresses rejection of allogeneic fetal rat pancreatic allografts. Transplant Proc 30(8):4092–4093

    Article  PubMed  Google Scholar 

  • Dupraz P et al (1999) Lentivirus-mediated Bcl-2 expression in betaTC-tet cells improves resistance to hypoxia and cytokine-induced apoptosis while preserving in vitro and in vivo control of insulin secretion. Gene Ther 6(6):1160–1169

    Article  CAS  PubMed  Google Scholar 

  • Falorni A et al (1996) Culture maintenance of isolated adult porcine pancreatic islets in three-dimensional gel matrices: morphologic and functional results. Pancreas 12(3):221–229

    Article  CAS  PubMed  Google Scholar 

  • Feng X et al (2000) Inducible nitric oxide synthetase is expressed in adult but not fetal pig pancreatic islets. Xenotransplantation 7(3):197–205

    Article  CAS  PubMed  Google Scholar 

  • Fernandes JR et al (2004) Transplantation of islets transduced with CTLA4-Ig and TGFbeta using adenovirus and lentivirus vectors. Transpl Immunol 13(3):191–200

    Article  CAS  PubMed  Google Scholar 

  • Fodor A et al (2007) Adult rat liver cells transdifferentiated with lentiviral IPF1 vectors reverse diabetes in mice: an ex vivo gene therapy approach. Diabetologia 50(1):121–130

    Article  CAS  PubMed  Google Scholar 

  • Franceschi RT, Ge C (2008) Gene delivery by adenoviruses. Methods Mol Biol 455:137–147

    Article  CAS  PubMed  Google Scholar 

  • Georgiou HM et al (1997) Genetic modification of an islet tumor cell line inhibits its rejection. Transplant Proc 29(1–2):1032–1033

    Article  CAS  PubMed  Google Scholar 

  • Gerace D et al (2013) Pancreatic transdifferentiation in porcine liver following lentiviral delivery of human furin-cleavable insulin. Transplant Proc 45(5):1869–1874

    Article  CAS  PubMed  Google Scholar 

  • Giannoukakis N et al (2000) Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Gene Ther 7(23):2015–2022

    Article  CAS  PubMed  Google Scholar 

  • Ginn SL et al (2004) 405. Efficient lentivirus vector-mediated transduction of neonatal porcine islet cell clusters: a powerful tool for xenotransplantation research. Mol Ther 9(S1):S155–S156

    Google Scholar 

  • Glaser B (2007) Type 2 diabetes: hypoinsulinism, hyperinsulinism, or both? PLoS Med 4(4):e148

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Golden B et al (2005) Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes. J Clin Endocrinol Metab 90(8):4904–4911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grey ST et al (1999) A20 inhibits cytokine-induced apoptosis and nuclear factor kappaB-dependent gene activation in islets. J Exp Med 190(8):1135–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grinberg-Bleyer Y et al (2010) IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J Exp Med 207(9):1871–1878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groth CG et al (1998) Pig-to-human islet transplantation. Transplant Proc 30(7):3809–3810

    Article  CAS  PubMed  Google Scholar 

  • Gubitosi-Klug RA (2014) The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: summary and future directions. Diabetes Care 37(1):44–49

    Article  PubMed  Google Scholar 

  • Halban PA et al (2001) Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high must the standards be set? Diabetes 50(10):2181–2191

    Article  CAS  PubMed  Google Scholar 

  • Hamaguchi K, Gaskins HR, Leiter EH (1991) NIT-1, a pancreatic beta-cell line established from a transgenic NOD/Lt mouse. Diabetes 40(7):842–849

    Article  CAS  PubMed  Google Scholar 

  • Hawthorne WJ (2014) STATE OF THE ART 4: Janssen-Cilag symposium: islet xenotransplantation—update. Immunol Cell Biol 92:A1–A29

    Article  Google Scholar 

  • Hawthorne WJ et al (2000) A large-animal model to evaluate the clinical potential of fetal pig pancreas fragment transplantation. Cell Transplant 9(6):867–875

    CAS  PubMed  Google Scholar 

  • Hawthorne WJ et al (2011) Pre-clinical model of composite foetal pig pancreas fragment/renal xenotransplantation to treat renal failure and diabetes. Xenotransplantation 18(6):390–399

    Article  PubMed  Google Scholar 

  • Hawthorne W et al (2014) Survival of genetically modified porcine neonatal islet xenografts in baboons. Transplantation 98:414

    Google Scholar 

  • He Z et al (2006) Long-term gene expression and metabolic control exerted by lentivirus-transduced pancreatic islets. Xenotransplantation 13(3):195–203

    Article  PubMed  Google Scholar 

  • Hering BJ et al (2006) Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med 12(3):301–303

    Article  CAS  PubMed  Google Scholar 

  • Holm P et al (2004) Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families. Diabetes 53(6):1584–1591

    Article  CAS  PubMed  Google Scholar 

  • Hsu PY, Kotin RM, Yang YW (2008) Glucose- and metabolically regulated hepatic insulin gene therapy for diabetes. Pharm Res 25(6):1460–1468

    Article  CAS  PubMed  Google Scholar 

  • Hu ZQ et al (1994) Mast cells display natural suppressor activity partially by releasing transforming growth factor-beta. Immunology 82(3):482–486

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs-Tulleneers-Thevissen D et al (2013) Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia 56(7):1605–1614

    Article  CAS  PubMed  Google Scholar 

  • Jimenez-Vera E, Davies S, Phillips P, O’Connell PJ, Hawthorne WJ (2015) Long-term cultured neonatal islet cell clusters demonstrate better outcomes for reversal of diabetes: in-vivo and molecular profiles. Xenotransplantation 22:114–123

    Google Scholar 

  • Johnson MC et al (2013) beta-cell-specific IL-2 therapy increases islet Foxp3 + Treg and suppresses type 1 diabetes in NOD mice. Diabetes 62(11):3775–3784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karamitsos DT (2011) The story of insulin discovery. Diabetes Res Clin Pract 93(Suppl 1):S2–S8

    Article  CAS  PubMed  Google Scholar 

  • Katagi M et al (2014) Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and their progeny in diabetic neuropathy. FEBS Lett 588(6):1080–1086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawabata K, Tashiro K, Mizuguchi H (2010) Differentiation of functional cells from iPS cells by efficient gene transfer. Yakugaku Zasshi 130(11):1527–1534

    Article  CAS  PubMed  Google Scholar 

  • Kawamoto K et al (2008) Prolonged survival of pig islets xenograft by adenovirus-mediated expression of either the membrane-bound human FasL or the human decoy Fas antigen gene. Xenotransplantation 15(5):333–343

    Article  PubMed  Google Scholar 

  • Kin T et al (2005) Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets. Diabetes 54(4):1032–1039

    Article  CAS  PubMed  Google Scholar 

  • Klein D et al (2000) Inhibition of Fas-mediated apoptosis in mouse insulinoma betaTC-3 cells via an anti-Fas ribozyme. Hum Gene Ther 11(7):1033–1045

    Article  CAS  PubMed  Google Scholar 

  • Kodama K et al (2008) Tissue- and age-specific changes in gene expression during disease induction and progression in NOD mice. Clin Immunol 129(2):195–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koizumi M et al (2006) Forced expression of PDX-1 induces insulin production in intestinal epithelia. Surgery 140(2):273–280

    Article  PubMed  Google Scholar 

  • Kojima S et al (2009) Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides 30(5):962–966

    Article  CAS  PubMed  Google Scholar 

  • Korbutt GS et al (1996) Large scale isolation, growth, and function of porcine neonatal islet cells. J Clin Invest 97(9):2119–2129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korsgren O et al (1991) Functional and morphological differentiation of fetal porcine islet-like cell clusters after transplantation into nude mice. Diabetologia 34(6):379–386

    Article  CAS  PubMed  Google Scholar 

  • Lam VW et al (2010) Evolution of pancreas transplant surgery. ANZ J Surg 80(6):411–418

    Article  PubMed  Google Scholar 

  • Lee KM et al (2014) TGF-beta-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol 44(6):1728–1736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lei P et al (2007) Efficient production of bioactive insulin from human epidermal keratinocytes and tissue-engineered skin substitutes: implications for treatment of diabetes. Tissue Eng 13(8):2119–2131

    Article  CAS  PubMed  Google Scholar 

  • Leibowitz G et al (1999) Gene transfer to human pancreatic endocrine cells using viral vectors. Diabetes 48(4):745–753

    Article  CAS  PubMed  Google Scholar 

  • Levine F (1997) Gene therapy for diabetes: strategies for beta-cell modification and replacement. Diabetes Metab Rev 13(4):209–246

    Article  CAS  PubMed  Google Scholar 

  • Liu YP, Berkhout B (2014) HIV-1-based lentiviral vectors. Methods Mol Biol 1087:273–284

    Article  CAS  PubMed  Google Scholar 

  • Loganathan G et al (2014) Pretreatment of donor pigs with a diet rich in soybean oil increases the yield of isolated islets. Transplant Proc 46(6):1945–1949

    Article  CAS  PubMed  Google Scholar 

  • Lu Y (2004) Recombinant adeno-associated virus as delivery vector for gene therapy–a review. Stem Cells Dev 13(1):133–145

    Article  CAS  PubMed  Google Scholar 

  • MacKenzie DA, Hullett DA, Sollinger HW (2003) Xenogeneic transplantation of porcine islets: an overview. Transplantation 76(6):887–891

    Article  PubMed  Google Scholar 

  • Mandel TE, Koulmanda M (1995) Xenotransplantation of fetal pig pancreas and reversal of diabetes in spontaneously diabetic NOD mice. Transplant Proc 27(3):2179–2180

    CAS  PubMed  Google Scholar 

  • Manolios N et al (1997) T-cell antigen receptor transmembrane peptides modulate T-cell function and T cell-mediated disease. Nat Med 3(1):84–88

    Article  CAS  PubMed  Google Scholar 

  • McCulloch D (2007) Classification of diabetes mellitus and genetic diabetic syndromes. In: Rose B (ed) UpToDate. UpToDate: Waltham, MA

    Google Scholar 

  • Meagher C et al (2007) CCL4 protects from type 1 diabetes by altering islet beta-cell-targeted inflammatory responses. Diabetes 56(3):809–817

    Article  CAS  PubMed  Google Scholar 

  • Mia S et al (2014) An optimized protocol for human M2 macrophages using M-CSF and IL-4/IL-10/TGF-beta yields a dominant immunosuppressive phenotype. Scand J Immunol 79(5):305–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitanchez D et al (1997) Glucose-stimulated genes and prospects of gene therapy for type I diabetes. Endocr Rev 18(4):520–540

    CAS  PubMed  Google Scholar 

  • Miyagawa S et al (2010) Complement regulation in the GalT KO era. Xenotransplantation 17(1):11–25

    Article  PubMed  Google Scholar 

  • Miyazaki J et al (1990) Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms. Endocrinology 127(1):126–132

    Article  CAS  PubMed  Google Scholar 

  • Moberg L et al (2002) Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 360(9350):2039–2045

    Article  CAS  PubMed  Google Scholar 

  • Moore HP et al (1983) Expressing a human proinsulin cDNA in a mouse ACTH-secreting cell. Intracellular storage, proteolytic processing, and secretion on stimulation. Cell 35(2 Pt 1):531–538

    Article  CAS  PubMed  Google Scholar 

  • Morrissey PE, Monaco AP (2014) Donation after circulatory death: current practices, ongoing challenges, and potential improvements. Transplantation 97(3):258–264

    Article  PubMed  Google Scholar 

  • Naldini L (2011) Ex vivo gene transfer and correction for cell-based therapies. Nat Rev Genet 12(5):301–315

    Article  CAS  PubMed  Google Scholar 

  • Nankivell BJ et al (1997) Recovery of diabetic neuropathy after pancreas transplantation. Transplant Proc 29(1–2):658–659

    Article  CAS  PubMed  Google Scholar 

  • Nayerossadat N, Maedeh T, Ali PA (2012) Viral and nonviral delivery systems for gene delivery. Adv Biomed Res 1:27

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Niu L et al (2008) Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene. World J Gastroenterol 14(26):4209–4215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nottle MB et al (2007) Production of homozygous alpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer. Xenotransplantation 14(4):339–344

    Article  PubMed  Google Scholar 

  • O’Connell PJ et al (2006) Clinical islet transplantation in type 1 diabetes mellitus: results of Australia’s first trial. Med J Aust 184(5):221–225

    PubMed  Google Scholar 

  • O’Connell PJ et al (2013) Transplantation of xenogeneic islets: are we there yet? Curr Diab Rep 13(5):687–694

    Article  PubMed  CAS  Google Scholar 

  • Olson DE et al (2008) Hepatic insulin gene therapy normalizes diurnal fluctuation of oxidative metabolism in diabetic BB/Wor rats. Mol Ther 16(7):1235–1242

    Article  CAS  PubMed  Google Scholar 

  • Ozmen L et al (2002) Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes 51(6):1779–1784

    Article  CAS  PubMed  Google Scholar 

  • Panakanti R, Mahato RI (2009) Bipartite adenoviral vector encoding hHGF and hIL-1Ra for improved human islet transplantation. Pharm Res 26(3):587–596

    Article  CAS  PubMed  Google Scholar 

  • Plesner A et al (2010) XIAP inhibition of beta-cell apoptosis reduces the number of islets required to restore euglycemia in a syngeneic islet transplantation model. Islets 2(1):18–23

    Article  PubMed  Google Scholar 

  • Prud’homme GJ, Draghia-Akli R, Wang Q (2007) Plasmid-based gene therapy of diabetes mellitus. Gene Ther 14(7):553–564

    Article  PubMed  CAS  Google Scholar 

  • Rabinovitch A et al (1999) Transfection of human pancreatic islets with an anti-apoptotic gene (bcl-2) protects beta-cells from cytokine-induced destruction. Diabetes 48(6):1223–1229

    Article  CAS  PubMed  Google Scholar 

  • Rafeullah N, Cackett N, Hussain K (2012) Fasting hypoglycaemia and postprandial hyperglycaemia as a prodrome of type 1 diabetes mellitus. Horm Res Paediatr 78(5–6):332–335

    Article  CAS  PubMed  Google Scholar 

  • Rahmati S, Alijani N, Kadivar M (2013) In vitro generation of glucose-responsive insulin producing cells using lentiviral based pdx-1 gene transduction of mouse (C57BL/6) mesenchymal stem cells. Biochem Biophys Res Commun 437(3):413–419

    Article  CAS  PubMed  Google Scholar 

  • Ravassard P et al (2011) A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion. J Clin Invest 121(9):3589–3597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren B et al (2007) Long-term correction of diabetes in rats after lentiviral hepatic insulin gene therapy. Diabetologia 50(9):1910–1920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren B et al (2013) Long-term reversal of diabetes in non-obese diabetic mice by liver-directed gene therapy. J Gene Med 15(1):28–41

    Article  CAS  PubMed  Google Scholar 

  • Rood PP et al (2005) Preformed antibodies to alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig cells in humans, baboons, and monkeys: implications for xenotransplantation. Transplant Proc 37(8):3514–3515

    Article  CAS  PubMed  Google Scholar 

  • Sachs DH, Galli C (2009) Genetic manipulation in pigs. Curr Opin Organ Transplant 14(2):148–153

    Article  PubMed  PubMed Central  Google Scholar 

  • Sadeghi H et al (2002) Genetic fusion of human insulin B-chain to the B-subunit of cholera toxin enhances in vitro antigen presentation and induction of bystander suppression in vivo. Immunology 106(2):237–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scalea J et al (2012) T-cell-mediated immunological barriers to xenotransplantation. Xenotransplantation 19(1):23–30

    Article  PubMed  PubMed Central  Google Scholar 

  • Schambach A et al (2013) Biosafety features of lentiviral vectors. Hum Gene Ther 24(2):132–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scharfmann R et al (2014) Development of a conditionally immortalized human pancreatic beta cell line. J Clin Invest 124(5):2087–2098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selden RF et al (1987) Regulation of insulin-gene expression. Implications for gene therapy. N Engl J Med 317(17):1067–1076

    Article  CAS  PubMed  Google Scholar 

  • Shahrestani S WA, Lam VW, Yuen L, Ryan B, Pleass HC, Hawthorne WJ (2016) Outcomes from pancreatic transplantation in donation after cardiac death: a systematic review and meta-analysis. Transplantation 2016, Mar 4. [Epub ahead of print] PMID: 26950713

    Google Scholar 

  • Shapiro AM et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355(13):1318–1330

    Article  CAS  PubMed  Google Scholar 

  • Shternhall-Ron K et al (2007) Ectopic PDX-1 expression in liver ameliorates type 1 diabetes. J Autoimmun 28(2–3):134–142

    Article  CAS  PubMed  Google Scholar 

  • Sigalla J et al (1997) Adenovirus-mediated gene transfer into isolated mouse adult pancreatic islets: normal beta-cell function despite induction of an anti-adenovirus immune response. Hum Gene Ther 8(13):1625–1634

    Article  CAS  PubMed  Google Scholar 

  • Sobel DO, Henzke A, Abbassi V (2010) Cyclosporin and methotrexate therapy induces remission in type 1 diabetes mellitus. Acta Diabetol 47(3):243–250

    Article  CAS  PubMed  Google Scholar 

  • Soltani N et al (2007) In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes. Gene Ther 14(12):981–988

    Article  CAS  PubMed  Google Scholar 

  • Sun JB, Holmgren J, Czerkinsky C (1994) Cholera toxin B subunit: an efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance. Proc Natl Acad Sci USA 91(23):10795–10799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutherland RM et al (2000) Protective effect of CTLA4Ig secreted by transgenic fetal pancreas allografts. Transplantation 69(9):1806–1812

    Article  CAS  PubMed  Google Scholar 

  • Talebi S et al (2012) Derivation of islet-like cells from mesenchymal stem cells using PDX1-transducing lentiviruses. Biotechnol Appl Biochem 59(3):205–212

    Article  CAS  PubMed  Google Scholar 

  • Tang DQ et al (2013) Genetically reprogrammed, liver-derived insulin-producing cells are glucose-responsive, but susceptible to autoimmune destruction in settings of murine model of type 1 diabetes. Am J Transl Res 5(2):184–199

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson DM et al (2011a) Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 91(3):373–378

    Article  PubMed  Google Scholar 

  • Thompson P et al (2011b) Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. Am J Transplant 11(12):2593–2602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson P et al (2012) Alternative immunomodulatory strategies for xenotransplantation: CD40/154 pathway-sparing regimens promote xenograft survival. Am J Transplant 12(7):1765–1775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thwaites SE et al (2012) Excellent outcomes of simultaneous pancreas kidney transplantation in patients from rural and urban Australia: a national service experience. Transplantation 94(12):1230–1235

    Article  PubMed  Google Scholar 

  • Tian C et al (2007) Induction of robust diabetes resistance and prevention of recurrent type 1 diabetes following islet transplantation by gene therapy. J Immunol 179(10):6762–6769

    Article  CAS  PubMed  Google Scholar 

  • Tian J et al (2008) Regulated insulin delivery from human epidermal cells reverses hyperglycemia. Mol Ther 16(6):1146–1153

    Article  CAS  PubMed  Google Scholar 

  • Tiwari JL et al (2012) Islet cell transplantation in type 1 diabetes: an analysis of efficacy outcomes and considerations for trial designs. Am J Transplant 12(7):1898–1907

    Article  CAS  PubMed  Google Scholar 

  • Torchilin VP (2006) Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng 8:343–375

    Article  CAS  PubMed  Google Scholar 

  • Toso C et al (2000) Isolation of adult porcine islets of Langerhans. Cell Transplant 9(3):297–305

    CAS  PubMed  Google Scholar 

  • Tuduri E, Bruin JE, Kieffer TJ (2012) Restoring insulin production for type 1 diabetes. J Diabetes 4(4):319–331

    Article  CAS  PubMed  Google Scholar 

  • Vågesjö E, Christoffersson G, Waldén TB, Carlsson PO, Essand M, Korsgren O, Phillipson M (2015) Immunological shielding by induced recruitment of regulatory T-lymphocytes delays rejection of islets transplanted to muscle. Cell Transplant 24(2):263–276

    Google Scholar 

  • van der Windt DJ et al (2009) Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am J Transplant 9(12):2716–2726

    Article  PubMed  CAS  Google Scholar 

  • Vizzardelli C et al (2002) Neonatal porcine pancreatic cell clusters as a potential source for transplantation in humans: characterization of proliferation, apoptosis, xenoantigen expression and gene delivery with recombinant AAV. Xenotransplantation 9(1):14–24

    Article  PubMed  Google Scholar 

  • Voltarelli JC et al (2007) Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 297(14):1568–1576

    Article  CAS  PubMed  Google Scholar 

  • Waldron-Lynch F, Herold KC (2011) Immunomodulatory therapy to preserve pancreatic beta-cell function in type 1 diabetes. Nat Rev Drug Discov 10(6):439–452

    Article  CAS  PubMed  Google Scholar 

  • Wirth T, Parker N, Yla-Herttuala S (2013) History of gene therapy. Gene 525(2):162–169

    Article  CAS  PubMed  Google Scholar 

  • Xia J et al (2011) Evaluation of biolistic gene transfer methods in vivo using non-invasive bioluminescent imaging techniques. BMC Biotechnol 11:62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J et al (2007) Reversal of diabetes in mice by intrahepatic injection of bone-derived GFP-murine mesenchymal stem cells infected with the recombinant retrovirus-carrying human insulin gene. World J Surg 31(9):1872–1882

    Article  PubMed  Google Scholar 

  • Xu AJ et al (2010) Effects of adenovirus-mediated interleukin-10 gene transfer on apoptosis and insulin secretion function of beta cell. Zhonghua Yi Xue Za Zhi 90(24):1711–1715

    CAS  PubMed  Google Scholar 

  • Yi S et al (2003) T cell-activated macrophages are capable of both recognition and rejection of pancreatic islet xenografts. J Immunol 170(5):2750–2758

    Article  CAS  PubMed  Google Scholar 

  • Yi S et al (2005) Involvement of CCR5 signaling in macrophage recruitment to porcine islet xenografts. Transplantation 80(10):1468–1475

    Article  CAS  PubMed  Google Scholar 

  • Yi S et al (2012) Adoptive transfer with in vitro expanded human regulatory T cells protects against porcine islet xenograft rejection via interleukin-10 in humanized mice. Diabetes 61(5):1180–1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon KH et al (1999) Differentiation and expansion of beta cell mass in porcine neonatal pancreatic cell clusters transplanted into nude mice. Cell Transplant 8(6):673–689

    CAS  PubMed  Google Scholar 

  • Zhang Y et al (2008) Genetically engineered K cells provide sufficient insulin to correct hyperglycemia in a nude murine model. Acta Biochim Biophys Sin (Shanghai) 40(2):149–157

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Westmead Clinical School, University of Sydney, Westmead Hospital, Westmead, NSW, 2145, Australia

    Wayne John Hawthorne

  2. National Pancreas and Islet Transplant Laboratories, The Westmead Institute for Medical Research, Westmead, NSW, 2145, Australia

    Wayne John Hawthorne

Authors
  1. Wayne John Hawthorne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wayne John Hawthorne .

Editor information

Editors and Affiliations

  1. NHMRC Clinical Trials Centre Diabetes and Islet-biology Group, The University of Sydney Faculty of Medicine, Sydney, New South Wales, Australia

    Anandwardhan A. Hardikar

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Hawthorne, W.J. (2016). Beta Cell Therapies for Type 1 Diabetes. In: A. Hardikar, A. (eds) Pancreatic Islet Biology. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-45307-1_12

Download citation

Publish with us

Policies and ethics

Search

Navigation