Current Diabetes Reports

, 8:324

Current challenges in islet transplantation

  • Cristiane B. Leitão
  • Pablo Cure
  • Thipaporn Tharavanij
  • David A. Baidal
  • Rodolfo Alejandro


Allogeneic islet transplantation is becoming a treatment option for patients with unstable type 1 diabetes mellitus (T1DM). Around 80% of the islet recipients achieve insulin independence after one or two islet infusions under “Edmonton-like” immunosuppressive protocol, but only 10% will remain insulin independent over the long term. Islet transplantation leads to glucose stabilization, and severe hypoglycemia is prevented even in patients back on insulin injections. Thus, islet transplantation has achieved the proposed targets in patients with unstable T1DM: normalizing blood glucose and hemoglobin A1c, preventing severe hypoglycemic episodes, and improving quality of life. The current aims of islet transplantation programs are to maintain the success achieved and to overcome remaining obstacles and limitations.

References and Recommended Reading

  1. 1.
    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group [no authors listed]. N Engl J Med 1993, 329:977–986.Google Scholar
  2. 2.
    Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group [no authors listed]. Diabetes 1997, 46:271–286.Google Scholar
  3. 3.
    Gruessner RW, Sutherland DE, Kandaswamy R, Gruessner AC: Over 500 solitary pancreas transplants in nonuremic patients with brittle diabetes mellitus. Transplantation 2008, 85:42–47.PubMedGoogle Scholar
  4. 4.
    Robertson RP: Islet transplantation as a treatment for diabetes — a work in progress. N Engl J Med 2004, 350:694–705.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    Shapiro AM, Ricordi C, Hering BJ, et al.: International trial of the Edmonton protocol for islet transplantation. N Engl J Med 2006, 355:1318–1330.PubMedCrossRefGoogle Scholar
  7. 7.
    Ryan EA, Paty BW, Senior PA, et al.: Five-year follow-up after clinical islet transplantation. Diabetes 2005, 54:2060–2069.PubMedCrossRefGoogle Scholar
  8. 8.
    Froud T, Ricordi C, Baidal DA, et al.: Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant 2005, 5:2037–2046.PubMedCrossRefGoogle Scholar
  9. 9.
    Poggioli R, Faradji RN, Ponte G, et al.: Quality of life after islet transplantation. Am J Transplant 2006, 6:371–378.PubMedCrossRefGoogle Scholar
  10. 10.
    Wonnacott K: Update on regulatory issues in pancreatic islet transplantation. Am J Ther 2005, 12:600–604.PubMedCrossRefGoogle Scholar
  11. 11.
    Stegall MD, Dean PG, Sung R, et al.: The rationale for the new deceased donor pancreas allocation schema. Transplantation 2007, 83:1156–1161.PubMedCrossRefGoogle Scholar
  12. 12.
    Shapiro AM, Sutherland DE: The new deceased donor pancreas allocation schema: do the recommendations go far enough? Transplantation 2007, 83:1151–1152.PubMedCrossRefGoogle Scholar
  13. 13.
    Ponte GM, Pileggi A, Messinger S, et al.: Toward maximizing the success rates of human islet isolation: influence of donor and isolation factors. Cell Transplant 2007, 16:595–607.PubMedGoogle Scholar
  14. 14.
    Lakey JR, Warnock GL, Rajotte RV, et al.: Variables in organ donors that affect the recovery of human islets of Langerhans. Transplantation 1996, 61:1047–1053.PubMedCrossRefGoogle Scholar
  15. 15.
    Caballero-Corbalan J, Eich T, Lundgren T, et al.: No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation. Transplantation 2007, 84:864–869.PubMedGoogle Scholar
  16. 16.
    Ricordi C, Fraker C, Szust J, et al.: Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to the cold-storage solution. Transplantation 2003, 75:1524–1527.PubMedCrossRefGoogle Scholar
  17. 17.
    Ricordi C, Lacy PE, Scharp DW: Automated islet isolation from human pancreas. Diabetes 1989, 38(Suppl 1):140–142.PubMedGoogle Scholar
  18. 18.
    Ichii H, Pileggi A, Molano RD, et al.: Rescue purification maximizes the use of human islet preparations for transplantation. Am J Transplant 2005, 5:21–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Ichii H, Sakuma Y, Pileggi A, et al.: Shipment of human islets for transplantation. Am J Transplant 2007, 7:1010–1020.PubMedCrossRefGoogle Scholar
  20. 20.
    Goss JA, Soltes G, Goodpastor SE, et al.: Pancreatic islet transplantation: the radiographic approach. Transplantation 2003, 76:199–203.PubMedCrossRefGoogle Scholar
  21. 21.
    Baidal DA, Froud T, Ferreira JV, et al.: The bag method for islet cell infusion. Cell Transplant 2003, 12:809–813.PubMedGoogle Scholar
  22. 22.
    Barshes NR, Lee TC, Goodpastor SE, et al.: Transaminitis after pancreatic islet transplantation. J Am Coll Surg 2005, 200:353–361.PubMedCrossRefGoogle Scholar
  23. 23.
    Collaborative Islet Transplant Registry (CITR). Available at Accessed February 2008.
  24. 24.
    Faradji RN, Monroy K, Messinger S, et al.: Simple measures to monitor beta-cell mass and assess islet graft dysfunction. Am J Transplant 2007, 7:303–308.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    Faradji RN, Monroy K, Riefkohl A, et al.: Continuous glucose monitoring system for early detection of graft dysfunction in allogenic islet transplant recipients. Transplant Proc 2006, 38:3274–3276.PubMedCrossRefGoogle Scholar
  27. 27.
    Hafiz MM, Faradji RN, Froud T, et al.: Immunosuppression and procedure-related complications in 26 patients with type 1 diabetes mellitus receiving allogeneic islet cell transplantation. Transplantation 2005, 80:1718–1728.PubMedCrossRefGoogle Scholar
  28. 28.
    Cure P, Pileggi A, Faradji RN, et al.: Cytomegalovirus infection in a recipient of solitary allogeneic islets. Am J Transplant 2006, 6(5 Pt 1):1089–1090.PubMedCrossRefGoogle Scholar
  29. 29.
    Maffi P, Angeli E, Bertuzzi F, et al.: Minimal focal steatosis of liver after islet transplantation in humans: a long-term study. Cell Transplant 2005, 14:727–733.PubMedCrossRefGoogle Scholar
  30. 30.
    Bhargava R, Senior PA, Ackerman TE, et al.: Prevalence of hepatic steatosis after islet transplantation and its relation to graft function. Diabetes 2004, 53:1311–1317.PubMedCrossRefGoogle Scholar
  31. 31.
    Markmann JF, Rosen M, Siegelman ES, et al.: Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes 2003, 52:1591–1594.PubMedCrossRefGoogle Scholar
  32. 32.
    Rafael E, Tibell A, Ryden M, et al.: Intramuscular autotransplantation of pancreatic islets in a 7-year-old child: a 2-year follow-up. Am J Transplant 2008, 8:458–462.PubMedGoogle Scholar
  33. 33.
    Larsen JL, Bennett RG, Burkman T, et al.: Tacrolimus and sirolimus cause insulin resistance in normal Sprague Dawley rats. Transplantation 2006, 82:466–470.PubMedCrossRefGoogle Scholar
  34. 34.
    Wyzgal J, Paczek L, Sanko-Resmer J, et al.: Insulin resistance in kidney allograft recipients treated with calcineurin inhibitors. Ann Transplant 2007, 12:26–29.PubMedGoogle Scholar
  35. 35.
    Bell E, Cao X, Moibi JA, et al.: Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets. Diabetes 2003, 52:2731–2739.PubMedCrossRefGoogle Scholar
  36. 36.
    Zhang N, Su D, Qu S, et al.: Sirolimus is associated with reduced islet engraftment and impaired beta-cell function. Diabetes 2006, 55:2429–2436.PubMedCrossRefGoogle Scholar
  37. 37.
    Zahr E, Molano RD, Pileggi A, et al.: Rapamycin impairs in vivo proliferation of islet beta-cells. Transplantation 2007, 84:1576–1583.PubMedCrossRefGoogle Scholar
  38. 38.
    Krebs M, Brunmair B, Brehm A, et al.: The Mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man. Diabetes 2007, 56:1600–1607.PubMedCrossRefGoogle Scholar
  39. 39.
    Paty BW, Harmon JS, Marsh CL, Robertson RP: Inhibitory effects of immunosuppressive drugs on insulin secretion from HIT-T15 cells and Wistar rat islets. Transplantation 2002, 73:353–357.PubMedCrossRefGoogle Scholar
  40. 40.
    Havrdova T, Saudek F, Boucek P, et al.: Metabolic effect of sirolimus versus mycophenolate mofetil on pancreatic graft function in the early posttransplant period. Transplant Proc 2005, 37:3544–3545.PubMedCrossRefGoogle Scholar
  41. 41.
    Han D, Xu X, Baidal D, et al.: Assessment of cytotoxic lymphocyte gene expression in the peripheral blood of human islet allograft recipients: elevation precedes clinical evidence of rejection. Diabetes 2004, 53:2281–2290.PubMedCrossRefGoogle Scholar
  42. 42.
    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.PubMedCrossRefGoogle Scholar
  43. 43.
    Fung MA, Warnock GL, Ao Z, et al.: The effect of medical therapy and islet cell transplantation on diabetic nephropathy: an interim report. Transplantation 2007, 84:17–22.PubMedCrossRefGoogle Scholar
  44. 44.
    Gillard P, Ling Z, Mathieu C, et al.: Comparison of sirolimus alone with sirolimus plus tacrolimus in type 1 diabetic recipients of cultured islet cell grafts. Transplantation 2008, 85:256–263.PubMedGoogle Scholar
  45. 45.
    Kawai T, Cosimi AB, Spitzer TR, et al.: HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008, 358:353–361.PubMedCrossRefGoogle Scholar
  46. 46.
    Mineo D, Ricordi C, Xu X, et al.: Combined islet and hematopoietic stem cell allotransplantation: a clinical pilot trial to induce chimerism and graft tolerance. Am J Transplant 2008 Apr 29 (Epub ahead of print).Google Scholar
  47. 47.
    Jaeger C, Brendel MD, Hering BJ, et al.: Progressive islet graft failure occurs significantly earlier in autoantibody-positive than in autoantibody-negative IDDM recipients of intrahepatic islet allografts. Diabetes 1997, 46:1907–1910.PubMedCrossRefGoogle Scholar
  48. 48.
    Xu G, Stoffers DA, Habener JF, Bonner-Weir S: Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999, 48:2270–2276.PubMedCrossRefGoogle Scholar
  49. 49.
    Campbell PM, Salam A, Ryan EA, et al.: Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation. Am J Transplant 2007, 7:1242–1248.PubMedCrossRefGoogle Scholar
  50. 50.
    Cardani R, Pileggi A, Ricordi C, et al.: Allosensitization of islet allograft recipients. Transplantation 2007, 84:1413–1427.PubMedGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  • Cristiane B. Leitão
  • Pablo Cure
  • Thipaporn Tharavanij
  • David A. Baidal
  • Rodolfo Alejandro
    • 1
  1. 1.Diabetes Research Institute-University of MiamiMiamiUSA

Personalised recommendations