State of the art of clinical islet transplantation and novel protocols of immunosuppression

Current Diabetes Reports

Volumn 11, Issue 5, 2011, Pages 345-354

  Shapiro, A M James ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Clinical Islet transplantation; Diabetes; Hypoglycemia; Immunosuppression; Islet of Langerhans; Transplantation

Indexed keywords

ALEMTUZUMAB; AUTOANTIBODY; BELATACEPT; BORTEZOMIB; CD40 ANTIGEN; CD40 LIGAND; COLLAGENASE; EFALIZUMAB; ETANERCEPT; FINGOLIMOD; HEMOGLOBIN A1C; HEPARIN; IMMUNOGLOBULIN; IMMUNOSUPPRESSIVE AGENT; INSULIN; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NEUTRAL PROTEINASE; RAPAMYCIN; RITUXIMAB; TACROLIMUS; THERMOLYSIN; THYMOCYTE ANTIBODY;

ANTICOAGULATION; APHERESIS; B LYMPHOCYTE; BIOASSAY; CARDIOVASCULAR RISK; CELL ISOLATION; DONOR SELECTION; DRUG DOSE TITRATION; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DYSLIPIDEMIA; FATIGUE; GLOMERULUS FILTRATION RATE; GRAFT REJECTION; HUMAN; HYPOGLYCEMIA; IMMUNOLOGICAL TOLERANCE; IMMUNOSUPPRESSIVE TREATMENT; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN TREATMENT; LIVER BIOPSY; LYMPHOPROLIFERATIVE DISEASE; MOUTH ULCER; MULTIPLE MYELOMA; MULTIPLE SCLEROSIS; NONHUMAN; OVARY CYST; PANCREAS ISLET TRANSPLANTATION; PATIENT SELECTION; PERCUTANEOUS HEPATIC PUNCTURE; PERIPHERAL EDEMA; PLASMAPHERESIS; PORTAL VEIN BLOOD PRESSURE; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PROTEINURIA; PSORIASIS; RECIPIENT; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; RISK BENEFIT ANALYSIS; RISK REDUCTION; SINGLE DRUG DOSE; SURGICAL RISK; T CELL DEPLETION;

EID: 80755189324     PISSN: 15344827     EISSN: 15390829     Source Type: Journal    
DOI: 10.1007/s11892-011-0217-8     Document Type: Review

References (59)

1. Skyler JS, Ricordi C. Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man. Diabetes. 2011;60(1):1-8. This current article nicely reviews a series of current efforts to reverse T1DM in patients.
2. McCall MD, Toso C, Baetge EE, Shapiro AM. Are stem cells a cure for diabetes? Clin Sci (Lond). 2010;118(2):87-97.
3. Bennet W, Sundberg B, Groth CG, Brendel MD, Brandhorst D, Brandhorst H, et al. Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes. 1999;48(10):1907-14. (Pubitemid 29458351)
4. Eriksson O, Eich T, Sundin A, Tibell A, Tufveson G, Andersson H, et al. Positron emission tomography in clinical islet transplantation. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. Am J Transplant. 2009;9(12):2816-24.
5. Harlan DM, Kenyon NS, Korsgren O, Roep BO. Current advances and travails in islet transplantation. Diabetes. 2009;58 (10):2175-84.
6. Koh A, Senior P, Salam A, Kin T, Imes S, Dinyari P et al. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation. 2010;89(4):465-71. This article demonstrates that peritransplant treatment of the islet transplant recipient with insulin and heparin can significantly improve the single-donor islet engraftment rate, and provides the first clinical supportive evidence that protection of islets from the IBMIR may improve islet survival, building upon substantial data generated by the Uppsala group in IBMIR research.
7. Korsgren O, Lundgren T, Felldin M, Foss A, Isaksson B, Permert J, et al. Optimising islet engraftment is critical for successful clinical islet transplantation. Diabetologia. 2008;51(2):227-32.
8. Korsgren O, Nilsson B. Improving islet transplantation: a road map for a widespread application for the cure of persons with type I diabetes. Curr Opin Organ Transplant. 2009;14(6):683-7.
9. Eich T, Eriksson O, Lundgren T. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med. 2007;356(26):2754-5. (Pubitemid 47001066)
10. Rickels MR, Collins HW, Naji A. Amyloid and transplanted islets. N Engl J Med. 2008;359(25):2729. author reply 31.
11. Westermark GT, Westermark P, Berne C, Korsgren O. Widespread amyloid deposition in transplanted human pancreatic islets. N Engl J Med. 2008;359(9):977-9.
12. Griffin SM, Alderson D, Farndon JR. Comparison of harvesting methods for islet transplantation. Br J Surg. 1986;73(9):712-5. (Pubitemid 16011172)
13. Bellin MD, Kandaswamy R, Parkey J, Zhang HJ, Liu B, Ihm SH et al. Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes. Am J Transplant. 2008;8 (11):2463-70. This article provides remarkable data from the Minnesota group on single-donor islet transplantation success in a clinical series of islet transplant recipients, in which Tdepletional induction therapy is given, combined with intensive peri-islet transplant management.
14. Bellin MD, Sutherland DE, Beilman GJ, Hong-McAtee I, Balamurugan AN, Hering BJ, et al. Similar islet function in islet allotransplant and autotransplant recipients, despite lower islet mass in autotransplants. Transplantation. 2011;91(3):367-72.
15. Shapiro AM, Toso C, Koh A, Calne RY, Kin T, O'Gornan D, et al. Alemtuzumab + Tac/MMF substantially improves long-term insulinindependence, and strongly suppresses auto + alloreactivity after clinical islet transplantation. Transplantation. 2010;90:134.
16. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230-8. This landmark article was the first to demonstrate sustained insulin independence for periods up to 1 year in seven T1DM subjects transplanted with human islets, and immunosuppressed with the "Edmonton Protocol," with sirolimus, tacrolimus, and an induction anti-interleukin-2 receptor mAb. Important for this success was the transplantation of islets prepared from at least two donor pancreas organs to provide sufficient islet engraftment mass. (Pubitemid 30490390)
17. Deng S, Markmann JF, Rickels M, Yeh H, Kim JI, Lian MM, et al. Islet alone versus islet after kidney transplantation: metabolic outcomes and islet graft survival. Transplantation. 2009;88(6):820-5.
18. Hammer M, Lammert M, Mejias SM, Kern W, Frier BM. Costs of managing severe hypoglycaemia in three European countries. J Med Econ. 2009;12(4):281-90.
19. Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the "dead-in-bed" syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr Pract. 2010;16(2):244-8. This article provides a case report of the use of continuous glucose monitoring, in which a patient died as a direct result of sustained and uncontrollable hypoglycemia. Although the "dead-in-bed" syndrome is fortunately rare, it remains a much feared and underestimated aspect of insulin injection treatment in T1DM.
20. Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995;18(11):1415.
21. Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008;57(12):3169-76.
22. Ryan EA, Shandro T, Green K, Paty BW, Senior PA, Bigam D, et al. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes. 2004;53(4):955-62. (Pubitemid 38436607)
23. Diabetes Control and Complications Trial (DCCT). Update. DCCT Research Group, Bethesda, Maryland. Diabetes Care. 1990;13(4):427-33.
24. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353 (25):2643-53. (Pubitemid 41817713)
25. Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant. 2004;4(12):2018-26. (Pubitemid 39611629)
26. Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. Jama. 2003;290 (21):2817-23. (Pubitemid 37509489)
27. Fiorina P, Gremizzi C, Maffi P, Caldara R, Tavano D, Monti L, et al. Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients. Diabetes Care. 2005;28(6):1358-65. (Pubitemid 40756697)
28. Fung MA, Warnock GL, Ao Z, Keown P, Meloche M, Shapiro RJ, et al. The effect of medical therapy and islet cell transplantation on diabetic nephropathy: an interim report. Transplantation. 2007;84 (1):17-22. (Pubitemid 47094636)
29. Senior PA, Paty BW, Cockfield SM, Ryan EA, Shapiro AM. Proteinuria developing after clinical islet transplantation resolves with sirolimus withdrawal and increased tacrolimus dosing. Am J Transplant. 2005;5(9):2318-23. (Pubitemid 41648484)
30. Thompson DM, Meloche M, Ao Z, Paty B, Keown P, Shapiro RJ et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation. 2011;91(3):373-8. This article demon- strates that successful islet transplantation can effectively reverse and stabilize risk of secondary diabetic complications in patients receiving islet transplantation. The Vancouver group compared islet recipients to best medical therapy (with optimal insulin, blood pressure, and lipid control) and found that the islet transplant intervention had a more positive impact upon secondary complication risk. The work now justifies a randomized controlled multicenter study.
31. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes. 1988;37 (4):413-20. (Pubitemid 18096377)
32. Lakey JR, Warnock GL, Shapiro AM, Korbutt GS, Ao Z, Kneteman NM, et al. Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion. Cell Transplant. 1999;8(3):285-92. (Pubitemid 29350224)
33. Barbaro B, Salehi P, Wang Y, Qi M, Gangemi A, Kuechle J, et al. Improved human pancreatic islet purification with the refined UIC-UB density gradient. Transplantation. 2007;84(9):1200-3. (Pubitemid 350125364)
34. Hering BJ, Kandaswamy R, Harmon JV, Ansite JD, Clemmings SM, Sakai T, et al. Transplantation of cultured islets from twolayer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant. 2004;4(3):390-401. (Pubitemid 38282295)
35. Hering BJ, Kandaswamy R, Ansite JD, Eckman PM, Nakano M, Sawada T, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. Jama. 2005;293(7):830-5. (Pubitemid 40250366)
36. Low G, Hussein N, Owen RJ, Toso C, Patel VH, Bhargava R, et al. Role of imaging in clinical islet transplantation. Radiographics. 2010;30(2):353-66.
37. Froud T, Yrizarry JM, Alejandro R, Ricordi C. Use of D-STAT to prevent bleeding following percutaneous transhepatic intraportal islet transplantation. Cell Transplant. 2004;13(1):55-9. (Pubitemid 38252713)
38. Villiger P, Ryan EA, Owen R, O'Kelly K, Oberholzer J, Saif FA, et al. Prevention of bleeding after islet transplantation: lessons learned from a multivariate analysis of 132 cases at a single institution. Am J Transplant. 2005;5(12):2992-8. (Pubitemid 43923962)
39. Markmann JF, Deng S, Huang X, Desai NM, Velidedeoglu EH, Lui C, et al. Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg. 2003;237 (6):741-9. discussion 9-50.
40. Gangemi A, Salehi P, Hatipoglu B, Martellotto J, Barbaro B, Kuechle JB, et al. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant. 2008;8(6):1250-61. (Pubitemid 351763686)
41. Posselt AM, Bellin MD, Tavakol M, Szot GL, Frassetto LA, Masharani U, et al. Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant. 2010;10(8):1870-80.
42. Burke GW, 3rd, Vendrame F, Pileggi A, Ciancio G, Reijonen H, Pugliese A. Recurrence of Autoimmunity Following Pancreas Transplantation. Curr Diab Rep. 2011. Recurrence of autoimmunity is a much underappreciated area in transplantation for T1DM. Burke et al. intensively studied evidence for and mechanisms underlying recurrence of autoimmunity following clinical pancreas transplantation, and their work is summarized here.
43. Matsumoto S, Takita M, Chaussabel D, Noguchi H, Shimoda M, Sugimoto K et al. Improving Efficacy of Clinical Islet Transplantation with Iodixanol Based Islet Purification, Thymoglobulin Induction and Blockage of IL-1-beta and TNF-alpha. Cell Transplant. 2011.
44. Ghofaili KA, Fung M, Ao Z, Meloche M, Shapiro RJ, Warnock GL, et al. Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes. Transplantation. 2007;83(1):24-8. (Pubitemid 46104966)
45. Merani S, Truong W, Emamaullee JA, Toso C, Knudsen LB, Shapiro AM. Liraglutide, a long-acting human glucagon-like peptide 1 analog, improves glucose homeostasis in marginal mass islet transplantation in mice. Endocrinology. 2008;149 (9):4322-8.
46. Toso C, McCall M, Emamaullee J, Merani S, Davis J, Edgar R, et al. Liraglutide, a long-acting human glucagon-like peptide 1 analogue, improves human islet survival in culture. Transpl Int. 2010;23(3):259-65.
47. Emamaullee JA, Davis J, Pawlick R, Toso C, Merani S, Cai SX et al. The caspase selective inhibitor EP1013 augments human islet graft function and longevity in marginal mass islet transplantation in mice. Diabetes. 2008;57(6):1556-66. Preventing cell death early after islet transplantation may facilitate single-donor islet transplant survival, as illustrated by Emamaullee et al. This paper demonstrates that transplantation of 10% of the usual required islet transplant mass may be sufficient to reverse diabetes in immunodeficient mice transplanted with human islets treated with a caspase inhibitor designed to prevent apoptosis.
48. McCallM, Toso C, Emamaullee J, Pawlick R, Edgar R, Davis J et al. The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice. Surgery.
49. Chatenoud L. Chemical immunosuppression in islet transplantation- friend or foe? N Engl J Med. 2008;358(11):1192-3.
50. Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117(9):2553-61. (Pubitemid 47494356)
51. Herold KC,Gitelman S,Greenbaum C, Puck J,HagopianW, Gottlieb P, et al. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009;132(2):166-73.
52. Wijkstrom M, Kenyon NS, Kirchhof N, Kenyon NM, Mullon C, Lake P, et al. Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD, and FTY720. Transplantation. 2004;77(6):827-35. (Pubitemid 38436818)
53. Posselt AM, Szot GL, Frassetto LA, Masharani U, Tavakol M, Amin R et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation. 2010;90(12):1595-601. The San Francisco group report their remarkable calcineurin-free immunosuppressive approaches in islet transplant recipients in which either anti-CD11a (efalizumab) or costimulation blockade with belatacept is given. The importance of these data are that effective immunosuppression can be supplied by regimens that do not contain nephrotoxic and diabetogenic calcineurin inhibitor drugs, and that the absence of tacrolimus can facilitate single-donor islet transplant engraftment and survival.
54. Liu C, Noorchashm H, Sutter JA, Naji M, Prak EL, Boyer J, et al. B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat Med. 2007;13 (11):1295-8. (Pubitemid 350073600)
55. Spitzer TR, Sykes M, Tolkoff-Rubin N, Kawai T, McAfee SL, Dey BR, et al. Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. Transplantation. 2011;91(6):672-6.
56. Matsumoto S, Okitsu T, Iwanaga Y, Noguchi H, Nagata H, Yonekawa Y, et al. Insulin independence after living-donor distal pancreatectomy and islet allotransplantation. Lancet. 2005;365 (9471):1642-4. (Pubitemid 40693414)
57. Sachs DH. Transplant tolerance: bench to bedside-26th annual samuel jason mixter lecture. Arch Surg. 2011;146(5):501-5.
58. Adams AB, Shirasugi N, Jones TR, Durham MM, Strobert EA, Cowan S, et al. Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival. J Immunol. 2005;174(1):542-50. (Pubitemid 40007445)
59. Thompson P, Cardona K, Russell M, Badell IR, Shaffer V, Korbutt G, et al. CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Am J Transplant. 2011;11(5):947-57.