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Erschienen in: Current Diabetes Reports 5/2011

01.10.2011

State of the Art of Clinical Islet Transplantation and Novel Protocols of Immunosuppression

verfasst von: A. M. James Shapiro

Erschienen in: Current Diabetes Reports | Ausgabe 5/2011

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Abstract

Clinical islet transplantation has transitioned from curiosity to realistic therapy over the past decade. An estimated 750 patients have undergone intraportal islet-alone transplantation over this period, and a smaller subset received combined islet-kidney transplants. The primary benefit of successful islet transplantation has been to eliminate severe, recurrent hypoglycemia, a problem that has been hard to eliminate by other means in 15% of those with type 1 diabetes. The secondary benefit of independence from insulin has attracted patients, but has had limited sustainability previously, especially with a single-donor graft, but recent results from four independent centers suggest marked improvement in long-term outcome, with 5-year results now approximating solitary pancreas transplantation. Emerging data confirm that islet transplantation can stabilize and reverse several secondary diabetic complications similar to whole pancreas transplantation, but larger, head-to-head trials are needed to compare islet transplantation with best medical therapies. Current goals are to extend durability, and to make islet transplantation more widely available for patients in need. Governmental and health insurance providers in several countries now reimburse islet transplantation as part of clinical care. As the safety of the procedure and of adjunctive immunosuppressive therapies improve, and benefit accrues over potential risk, islet transplantation will be offered earlier in the course of the disease, including newly diagnosed children. The role of islet transplantation in type 2 diabetes has yet to be defined. We review the current status of islet transplantation, and discuss current and future immunosuppressive protocols that will pave the way to more broad application of cellular replacement in diabetes.
Literatur
1.
Zurück zum Zitat • 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. PubMedCrossRef • 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. PubMedCrossRef
2.
Zurück zum Zitat McCall MD, Toso C, Baetge EE, Shapiro AM. Are stem cells a cure for diabetes? Clin Sci (Lond). 2010;118(2):87–97.CrossRef McCall MD, Toso C, Baetge EE, Shapiro AM. Are stem cells a cure for diabetes? Clin Sci (Lond). 2010;118(2):87–97.CrossRef
3.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
4.
Zurück zum Zitat 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. 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.
Zurück zum Zitat Harlan DM, Kenyon NS, Korsgren O, Roep BO. Current advances and travails in islet transplantation. Diabetes. 2009;58(10):2175–84.PubMedCrossRef Harlan DM, Kenyon NS, Korsgren O, Roep BO. Current advances and travails in islet transplantation. Diabetes. 2009;58(10):2175–84.PubMedCrossRef
6.
Zurück zum Zitat • 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. PubMedCrossRef • 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. PubMedCrossRef
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
9.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
10.
Zurück zum Zitat Rickels MR, Collins HW, Naji A. Amyloid and transplanted islets. N Engl J Med. 2008;359(25):2729. author reply −31.PubMedCrossRef Rickels MR, Collins HW, Naji A. Amyloid and transplanted islets. N Engl J Med. 2008;359(25):2729. author reply −31.PubMedCrossRef
11.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
12.
Zurück zum Zitat Griffin SM, Alderson D, Farndon JR. Comparison of harvesting methods for islet transplantation. Br J Surg. 1986;73(9):712–5.PubMedCrossRef Griffin SM, Alderson D, Farndon JR. Comparison of harvesting methods for islet transplantation. Br J Surg. 1986;73(9):712–5.PubMedCrossRef
13.
Zurück zum Zitat • 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 T-depletional induction therapy is given, combined with intensive peri-islet transplant management. PubMedCrossRef • 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 T-depletional induction therapy is given, combined with intensive peri-islet transplant management. PubMedCrossRef
14.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
15.
Zurück zum Zitat Shapiro AM, Toso C, Koh A, Calne RY, Kin T, O’Gornan D, et al. Alemtuzumab + Tac/MMF substantially improves long-term insulin-independence, and strongly suppresses auto + alloreactivity after clinical islet transplantation. Transplantation. 2010;90:134.CrossRef Shapiro AM, Toso C, Koh A, Calne RY, Kin T, O’Gornan D, et al. Alemtuzumab + Tac/MMF substantially improves long-term insulin-independence, and strongly suppresses auto + alloreactivity after clinical islet transplantation. Transplantation. 2010;90:134.CrossRef
16.
Zurück zum Zitat • 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. PubMedCrossRef • 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. PubMedCrossRef
17.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
18.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
19.
Zurück zum Zitat • 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. PubMedCrossRef • 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. PubMedCrossRef
20.
Zurück zum Zitat Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995;18(11):1415. Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995;18(11):1415.
21.
22.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
23.
Zurück zum Zitat Diabetes Control and Complications Trial (DCCT). Update. DCCT Research Group, Bethesda, Maryland. Diabetes Care. 1990;13(4):427–33. Diabetes Control and Complications Trial (DCCT). Update. DCCT Research Group, Bethesda, Maryland. Diabetes Care. 1990;13(4):427–33.
24.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
25.
Zurück zum Zitat Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant. 2004;4(12):2018–26.PubMedCrossRef Gruessner RW, Sutherland DE, Gruessner AC. Mortality assessment for pancreas transplants. Am J Transplant. 2004;4(12):2018–26.PubMedCrossRef
26.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
27.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
28.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
29.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
30.
Zurück zum Zitat • 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 demonstrates 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. PubMedCrossRef • 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 demonstrates 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. PubMedCrossRef
31.
Zurück zum Zitat Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes. 1988;37(4):413–20.PubMedCrossRef Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes. 1988;37(4):413–20.PubMedCrossRef
32.
Zurück zum Zitat 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.PubMed 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.PubMed
33.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
34.
Zurück zum Zitat Hering BJ, Kandaswamy R, Harmon JV, Ansite JD, Clemmings SM, Sakai T, et al. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant. 2004;4(3):390–401.PubMedCrossRef Hering BJ, Kandaswamy R, Harmon JV, Ansite JD, Clemmings SM, Sakai T, et al. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant. 2004;4(3):390–401.PubMedCrossRef
35.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
36.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
37.
Zurück zum Zitat 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.PubMed 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.PubMed
38.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
39.
Zurück zum Zitat 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.PubMed 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.PubMed
40.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
41.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
42.
Zurück zum Zitat • 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. • 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
45.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
46.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
47.
Zurück zum Zitat • 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. PubMedCrossRef • 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. PubMedCrossRef
48.
Zurück zum Zitat McCall M, 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. McCall M, 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.
Zurück zum Zitat Chatenoud L. Chemical immunosuppression in islet transplantation–friend or foe? N Engl J Med. 2008;358(11):1192–3.PubMedCrossRef Chatenoud L. Chemical immunosuppression in islet transplantation–friend or foe? N Engl J Med. 2008;358(11):1192–3.PubMedCrossRef
50.
Zurück zum Zitat Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117(9):2553–61.PubMedCrossRef Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117(9):2553–61.PubMedCrossRef
51.
Zurück zum Zitat Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, 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.PubMedCrossRef Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, 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.PubMedCrossRef
52.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
53.
Zurück zum Zitat • 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. PubMedCrossRef • 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. PubMedCrossRef
54.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
55.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
56.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
57.
Zurück zum Zitat Sachs DH. Transplant tolerance: bench to bedside–26th annual samuel jason mixter lecture. Arch Surg. 2011;146(5):501–5.PubMedCrossRef Sachs DH. Transplant tolerance: bench to bedside–26th annual samuel jason mixter lecture. Arch Surg. 2011;146(5):501–5.PubMedCrossRef
58.
Zurück zum Zitat 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.PubMed 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.PubMed
59.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
Metadaten
Titel
State of the Art of Clinical Islet Transplantation and Novel Protocols of Immunosuppression
verfasst von
A. M. James Shapiro
Publikationsdatum
01.10.2011
Verlag
Current Science Inc.
Erschienen in
Current Diabetes Reports / Ausgabe 5/2011
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-011-0217-8

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