Skip to main content

Advertisement

SpringerLink
Log in

Islet transplantation: Current status and future directions

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Pancreatic islet transplantation has gone a long way to finally enter the armamentarium of today’s clinicians for the battle against diabetes. The proof of principle has been made and current clinical islet transplant trials need to further refine this attractive treatment modality. We review the post-Edmonton era, the selection of islet transplant recipients, the production of islet grafts, and the need for immunosuppression and procedure-related risks. The success of islet transplantation and expansion of clinical trials with islet networks are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Bliss M, ed: The Discovery of Insulin. Chicago: The University of Chicago Press; 1982.

    Google Scholar 

  2. Shapiro AM, Lakey JR, Ryan EA, et al.: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000, 343:230–238. Describes the original Edmonton series of islet transplantation.

    Article  PubMed  CAS  Google Scholar 

  3. Ballinger WF, Lacy PE: Transplantation of intact pancreatic islets in rats. Surgery 1972, 72:175–186.

    PubMed  CAS  Google Scholar 

  4. Najarian JS, Sutherland DE, Matas AJ, et al.: Human islet transplantation: a preliminary report. Transplant Proc 1977, 9:233–236.

    PubMed  CAS  Google Scholar 

  5. Sutherland DE: Pancreas and islet transplantation. II. Clinical trials. Diabetologia 1981, 20:435–450.

    PubMed  CAS  Google Scholar 

  6. Largiader F, Kolb E, Binswanger U: A long-term functioning human pancreatic islet allotransplant. Transplantation 1980, 29:76–77.

    Article  PubMed  CAS  Google Scholar 

  7. Scharp DW, Lacy PE, Santiago JV, et al.: Insulin independence after islet transplantation into type I diabetic patient. Diabetes 1990, 39:515–518.

    Article  PubMed  CAS  Google Scholar 

  8. Alejandro R, Lehmann R, Ricordi C, et al.: Long-term function (6 years) of islet allografts in type 1 diabetes. Diabetes 1997, 46:1983–1989.

    Article  PubMed  CAS  Google Scholar 

  9. Oberholzer J, Triponez F, Mage R, et al.: Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations. Transplantation 2000, 69:1115–1123.

    Article  PubMed  CAS  Google Scholar 

  10. Brendel MD, Hering B, Schultz AO, Bretzel RG: International Islet Transplant Registry. Newsletter 8. Giessen, Germany: Justus-Liebig-University of Giessen; 2001.

    Google Scholar 

  11. Weber DJ, McFarland RD, Irony I: Selected Food and Drug Administration review issues for regulation of allogeneic islets of Langerhans as somatic cell therapy. Transplantation 2002, 74:1816–1820.

    Article  PubMed  Google Scholar 

  12. Weber DJ: FDA regulation of allogeneic islets as a biological product. Cell Biochem Biophys 2004, 40:19–22.

    Article  PubMed  Google Scholar 

  13. Shapiro AM, Ricordi C, Hering B: Edmonton’s islet success has indeed been replicated elsewhere. Lancet 2003, 362:1242.

    Article  PubMed  Google Scholar 

  14. Markmann JF, Deng S, Huang X, et al.: Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg 2003, 237:741–749; discussion 749–750.

    Article  PubMed  Google Scholar 

  15. Kaufman DB, Baker MS, Chen X, et al.: Sequential kidney/islet transplantation using prednisone-free immunosuppression. Am J Transplant 2002, 2:674–677.

    Article  PubMed  CAS  Google Scholar 

  16. Lehmann R, Weber M, Berthold P, et al.: Successful simultaneous islet-kidney transplantation using a steroid-free immunosuppression: two-year follow-up. Am J Transplant 2004, 4:1117–1123.

    Article  PubMed  CAS  Google Scholar 

  17. Berney T, Bucher P, Mathe Z, et al.: Islet of Langerhans allogeneic transplantation at the University of Geneva in the steroid free era in islet after kidney and simultaneous isletkidney transplantations. Transplant Proc 2004, 36:1121–1122.

    Article  PubMed  CAS  Google Scholar 

  18. Vantyghem MC, Hazzan M, Tourvieille S, et al.: Selection of diabetic patients for islet transplantation. A single-center experience. Diabetes Metab 2004, 30:417–423.

    Article  PubMed  CAS  Google Scholar 

  19. Ryan EA, Shandro T, Green K, et al.: Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 2004, 53:955–962. Analyzes the metabolic outcome after islet transplantation under the Edmonton protocol. Highlights the benefit of islet transplantation in controlling hypoglycemic episodes.

    Article  PubMed  CAS  Google Scholar 

  20. Smets YF, Westendorp RG, vander Pijl JW, et al.: Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure. Lancet 1999, 353:1915–1919.

    Article  PubMed  CAS  Google Scholar 

  21. Shapiro AM, Nanji SA, Lakey JR: Clinical islet transplant: current and future directions towards tolerance. Immunol Rev 2003, 196:219–236.

    Article  PubMed  CAS  Google Scholar 

  22. Matsumoto S, Kuroda Y: Perfluorocarbon for organ preservation before transplantation. Transplantation 2002, 74:1804–1809.

    Article  PubMed  CAS  Google Scholar 

  23. Tsujimura T, Kuroda Y, Avila JG, et al.: Influence of pancreas preservation on human islet isolation outcomes: impact of the two-layer method. Transplantation 2004, 78:96–100.

    Article  PubMed  Google Scholar 

  24. Hering BJ, Kandaswamy R, Harmon JV, et al.: Transplantation of Cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant 2004, 4:390–401.

    Article  PubMed  CAS  Google Scholar 

  25. Hering BJ, Kandaswamy R, Ansite JD, et al.: Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA 2005, 293:830–835. Presents proof of principle that single-donor islet transplants can achieve insulin independence. Highlights the importance of refining current clinical protocols.

    Article  PubMed  CAS  Google Scholar 

  26. Ono J, Lacy PE, Michael HE, Greider MH: Studies of the functional and morphologic status of islets maintained at 24 C for four weeks in vitro. Am J Pathol 1979, 97:489–503.

    PubMed  CAS  Google Scholar 

  27. Gaber AO, Fraga DW, Callicutt CS, et al.: Improved in vivo pancreatic islet function after prolonged in vitro islet culture. Transplantation 2001, 72:1730–1736.

    Article  PubMed  CAS  Google Scholar 

  28. Ault A: Edmonton’s islet success tough to duplicate elsewhere. Lancet 2003, 361:2054.

    PubMed  Google Scholar 

  29. Beattie GM, Montgomery AM, Lopez AD, et al.: A novel approach to increase human islet cell mass while preserving beta-cell function. Diabetes 2002, 51:3435–3439.

    Article  PubMed  CAS  Google Scholar 

  30. Burns CJ, Persaud SJ, Jones PM: Stem cell therapy for diabetes: do we need to make beta cells? J Endocrinol 2004, 183:437–443.

    Article  PubMed  CAS  Google Scholar 

  31. Hwang WS, Ryu YJ, Park JH, et al.: Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science 2004, 303:1669–1674.

    Article  PubMed  CAS  Google Scholar 

  32. Cowan CA, Klimanskaya I, McMahon J, et al.: Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med 2004, 350:1353–1356.

    Article  PubMed  CAS  Google Scholar 

  33. Rajagopal J, Anderson WJ, Kume S, et al.: Insulin staining of ES cell progeny from insulin uptake. Science 2003, 299:363.

    PubMed  Google Scholar 

  34. Hansson M, Tonning A, Frandsen U, et al.: Artifactual insulin release from differentiated embryonic stem cells. Diabetes 2004, 53:2603–2609.

    Article  PubMed  CAS  Google Scholar 

  35. Inzunza J, Gertow K, Stromberg MA, et al.: Derivation of human embryonic stem cell lines in serum replacement medium using postnatal human fibroblasts as feeder cells. Stem Cells 2005, 23:544–549.

    Article  PubMed  CAS  Google Scholar 

  36. Salmon P, Oberholzer J, Occhiodoro T, et al.: Reversible immortalization of human primary cells by lentivector-mediated transfer of specific genes. Mol Ther 2000, 2:404–414.

    Article  PubMed  CAS  Google Scholar 

  37. Kobayashi N, Fujiwara T, Westerman KA, et al.: Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes. Science 2000, 287:1258–1262.

    Article  PubMed  CAS  Google Scholar 

  38. Cudre-Mauroux C, Occhiodoro T, Konig S, et al.: Lentivectormediated transfer of Bmi-1 and telomerase in muscle satellite cells yields a duchenne myoblast cell line with long-term genotypic and phenotypic stability. Hum Gene Ther 2003, 14:1525–1533.

    Article  PubMed  CAS  Google Scholar 

  39. Nanji SA, Shapiro AM: Islet transplantation in patients with diabetes mellitus: choice of immunosuppression. BioDrugs 2004, 18:315–328.

    Article  PubMed  CAS  Google Scholar 

  40. Rother KI, Harlan DM: Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus. J Clin Invest 2004, 114:877–883.

    Article  PubMed  CAS  Google Scholar 

  41. Cure P, Pileggi A, Froud T, et al.: Alterations of the female reproductive system in recipients of islet grafts. Transplantation 2004, 78:1576–1581.

    Article  PubMed  Google Scholar 

  42. Venturini M, Angeli E, Maffi P, et al.: Technique, complications, and therapeutic efficacy of percutaneous transplantation of human pancreatic islet cells in type 1 diabetes: the role of US. Radiology 2005, 234:617–624.

    Article  PubMed  Google Scholar 

  43. Owen RJ, Ryan EA, O’Kelly K, et al.: Percutaneous transhepatic pancreatic islet cell transplantation in type 1 diabetes mellitus: radiologic aspects. Radiology 2003, 229:165–170.

    Article  PubMed  Google Scholar 

  44. Goss JA, Soltes G, Goodpastor SE, et al.: Pancreatic islet transplantation: the radiographic approach. Transplantation 2003, 76:199–203.

    Article  PubMed  Google Scholar 

  45. Bucher P, Mathe Z, Bosco D, et al.: Morbidity associated with intraportal islet transplantation. Transplant Proc 2004, 36:1119–1120.

    Article  PubMed  CAS  Google Scholar 

  46. Warnock GL, Kneteman NM, Ryan EA, et al.: Long-term followup after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1992, 35:89–95.

    Article  PubMed  CAS  Google Scholar 

  47. Hafiz MM, Poggioli R, Caulfield A, et al.: Cytomegalovirus prevalence and transmission after islet allograft transplant in patients with type 1 diabetes mellitus. Am J Transplant 2004, 4:1697–1702.

    Article  PubMed  Google Scholar 

  48. Barshes NR, Lee TC, Brunicardi FC, et al.: Lack of cytomegalovirus transmission after pancreatic islet transplantation. Cell Transplant 2004, 13:833–838.

    PubMed  Google Scholar 

  49. Fiorina P, Folli F, Zerbini G, et al.: Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants. J Am Soc Nephrol 2003, 14:2150–2158.

    Article  PubMed  Google Scholar 

  50. Ricordi C: Islet transplantation: a brave new world. Diabetes 2003, 52:1595–1603.

    Article  PubMed  CAS  Google Scholar 

  51. Ryan EA, Paty BW, Senior PA, et al.: Beta-score: an assessment of beta-cell function after islet transplantation. Diabetes Care 2005, 28:343–347.

    Article  PubMed  Google Scholar 

  52. Ryan EA, Lakey JR, Paty BW, et al.: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 2002, 51:2148–2157.

    Article  PubMed  CAS  Google Scholar 

  53. Cretin N, Caulfield A, Fournier B, et al.: Insulin independence and normalization of oral glucose tolerance test after islet cell allotransplantation. Transpl Int 2001, 14:343–345.

    Article  PubMed  CAS  Google Scholar 

  54. Ris F, Toso C, Veith FU, et al.: Are criteria for islet and pancreas donors sufficiently different to minimize competition? Am J Transplant 2004, 4:763–766.

    Article  PubMed  Google Scholar 

  55. Benhamou PY, Oberholzer J, Toso C, et al.: Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999–2000). Groupe de Recherche Rhin Rhjne Alpes Geneve pour la transplantation d’Ilots de Langerhans. Diabetologia 2001, 44:859–864.

    Article  PubMed  CAS  Google Scholar 

  56. Goss JA, Goodpastor SE, Brunicardi FC, et al.: Development of a human pancreatic islet-transplant program through a collaborative relationship with a remote islet-isolation center. Transplantation 2004, 77:462–466.

    Article  PubMed  Google Scholar 

  57. Langer RM, Mathe Z, Doros A, et al.: Successful islet after kidney transplantations in a distance over 1000 kilometres: preliminary results of the Budapest-Geneva collaboration. Transplant Proc 2004, 36:3113–3115.

    Article  PubMed  CAS  Google Scholar 

  58. Kessler L, Bucher P, Milliat-Guittard L, et al.: Influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients within the Swiss-French GRAGIL network. Transplantation 2004, 77:1301–1304.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Transplantation, University of Illinois, MC958, 840 South Wood Street, CSB Suite 402, 60093, Chicago, IL, USA

    José Oberholzer MD

Authors
  1. Betul Hatipoglu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enrico Benedetti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Oberholzer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hatipoglu, B., Benedetti, E. & Oberholzer, J. Islet transplantation: Current status and future directions. Curr Diab Rep 5, 311–316 (2005). https://doi.org/10.1007/s11892-005-0029-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-005-0029-9

Keywords

Search

Navigation