Immunological aspects of pancreatic islet cell transplantation

Expert Review of Clinical Immunology

Volumn 6, Issue 1, 2010, Pages 111-124

  Azzi, Jamil ^a   Geara, Abdallah S ^b   El Sayegh, Suzanne ^b   Abdi, Reza ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b STATEN ISLAND UNIVERSITY HOSPITAL   (United States)

Author keywords

Alloimmunity; IBMIR; Instant blood mediated inflammatory reaction; Islet cell transplantation; Recurrence of autoimmunity

Indexed keywords

ACTIVATED PROTEIN C; AZATHIOPRINE; CD39 ANTIGEN; COMPLEMENT RECEPTOR; CORTICOSTEROID; CYCLOSPORIN; DACLIZUMAB; DEXTRAN; ETANERCEPT; GLUCOSE; IMMUNOLOGICAL ADJUVANT; INSULIN; MELAGATRAN; NICOTINAMIDE; RAPAMYCIN; TACROLIMUS; TUMOR NECROSIS FACTOR ALPHA ANTIBODY;

ALLOIMMUNITY; AUTOIMMUNITY; BLOOD CLOTTING; CELL ENCAPSULATION; COMPLEMENT ACTIVATION; COMPLEMENT INHIBITION; CYTOKINE PRODUCTION; DONOR; ENGRAFTMENT; GLUCOSE HOMEOSTASIS; GRAFT REJECTION; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HEPARINIZATION; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATION; INSTANT BLOOD MEDIATED INFLAMMATORY REACTION; INSULIN DEPENDENT DIABETES MELLITUS; LIVER TOXICITY; MICROENCAPSULATION; OXIDATION; OXIDATIVE STRESS; PANCREAS ISLET TRANSPLANTATION; PANCREAS TRANSPLANTATION; PATHOPHYSIOLOGY; REVIEW;

ANIMALS; AUTOIMMUNITY; DIABETES MELLITUS, TYPE 1; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATION; INFLAMMATION MEDIATORS; ISLETS OF LANGERHANS TRANSPLANTATION; TIME FACTORS; TRANSPLANTATION TOLERANCE; TREATMENT OUTCOME;

EID: 77649159849     PISSN: 1744666X     EISSN: None     Source Type: Journal    
DOI: 10.1586/eci.09.67     Document Type: Review

References (167)

1. DIAMOND Project Group. Incidence and trends of childhood Type 1 diabetes worldwide 1990-1999. Diabet. Med. 23, 857-866 (2006).
2. Zipris D. Epidemiology of Type 1 diabetes and what animal models teach us about the role of viruses in disease mechanisms. Clin. Immunol. 131, 11-23 (2009).
3. Downing R. Historical review of pancreatic islet transplantation. World J. Surg. 8, 137-142 (1984).
4. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 61, 827-837 (1967).
5. Lacy PE, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35-39 (1967).
6. Ballinger WF, Lacy PE. Transplantation of intact pancreatic islets in rats. Surgery 72, 175-186 (1972).
7. Sutherland DE, Frenzel E, Payne WD, Matas AJ, Najarian JS. Transplantation of adult islet tissue in rats: spleen vs portal vein site. Surg. Forum. 30, 305-307 (1979).
8. Pyzdrowski KL, Kendall DM, Halter JB, Nakhleh RE, Sutherland DE, Robertson RP. Preserved insulin secretion and insulin independence in recipients of islet autografts. N. Engl. J. Med. 327, 220-226 (1992).
9. Sutherland DE. Report of International Human Pancreas and Islet Transplantation Registry Cases through 1981. Diabetes 31(Suppl. 4), 112-116 (1982).
10. Dobroschke J, Schwemmle K, Laube H, Langhoff G, Bretzel RG, Federlin K. Autotransplantation of Langerhans' islets in a case of total duodenopancreatectomy (author's translation). Langenbecks Arch. Chir. 350, 53-58 (1979). (Pubitemid 10204352)
11. Grodsinsky C, Malcom S, Goldman J, Dienst S, Oh HK, Westrick P. Islet cell autotransplantation after pancreatectomy for chronic pancreatitis. Its limitations. Arch. Surg. 116, 511-516 (1981).
12. Valente U, Ferro M, Campisi C et al. Report of clinical cases of islet autotransplantation. Transplant Proc. 12, 202-204 (1980). (Pubitemid 11177266)
13. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes 37, 413-420 (1988). (Pubitemid 18096377)
14. Scharp DW, Lacy PE, Santiago JV et al. Insulin independence after islet transplantation into Type I diabetic patient. Diabetes 39, 515-518 (1990).
15. Alejandro R, Mintz DH, Noel J et al. Islet cell transplantation in Type I diabetes mellitus. Transplant Proc. 19, 2359-2361 (1987).
16. Tzakis AG, Ricordi C, Alejandro R et al. Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet 336, 402-405 (1990).
17. 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. 343, 230-238 (2000).
18. Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE. Pancreas and islet transplantation in Type 1 diabetes. Diabetes Care 29, 935 (2006).
19. Ryan EA, Lakey JR, Rajotte RV et al. Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 50, 710-719 (2001).
20. Rickels MR, Schutta MH, Mueller R et al. Islet cell hormonal responses to hypoglycemia after human islet transplantation for Type 1 diabetes. Diabetes 54, 3205-3211 (2005).
21. Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR). Clin. Transpl. 45-56 (2008).
22. Ryan EA, Lakey JR, Paty BW et al. Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 51, 2148-2157 (2002).
23. Robertson RP. Islet transplantation as a treatment for diabetes - a work in progress. N. Engl. J. Med. 350, 694-705 (2004).
24. Bennet W, Sundberg B, Groth CG et al. Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes 48, 1907-1914 (1999).
25. Bennet W, Groth CG, Larsson R, Nilsson B, Korsgren O. 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, 125-133 (2000).
26. Eich T, Eriksson O, Lundgren T. Visualization of early engraftment in clinical islet transplantation by positronemission tomography. N. Engl. J. Med. 356, 2754-2755 (2007). (Pubitemid 47001066)
27. Griffith RC, Scharp DW, Hartman BK, Ballinger WF, Lacy PE. A morphologic study of intrahepatic portal-vein islet isografts. Diabetes 26, 201-214 (1977).
28. Hanley S, Liu S, Lipsett M et al. Tumor necrosis factor-a production by human islets leads to postisolation cell death. Transplantation 82, 813-818 (2006).
29. Johansson U, Olsson A, Gabrielsson S, Nilsson B, Korsgren O. Inflammatory mediators expressed in human islets of Langerhans: implications for islet transplantation. Biochem. Biophys. Res. Commun. 308, 474-479 (2003).
30. Piemonti L, Leone BE, Nano R et al. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Diabetes 51, 55-65 (2002).
31. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46, 1733-1742 (1997).
32. Tiedge M, Lortz S, Munday R, Lenzen S. Complementary action of antioxidant enzymes in the protection of bioengineered insulin-producing RINm5F cells against the toxicity of reactive oxygen species. Diabetes 47, 1578-1585 (1998).
33. Tiedge M, Lortz S, Munday R, Lenzen S. Protection against the co-operative toxicity of nitric oxide and oxygen free radicals by overexpression of antioxidant enzymes in bioengineered insulin-producing RINm5F cells. Diabetologia 42, 849-855 (1999).
34. Bertera S, Crawford ML, Alexander AM et al. Gene transfer of manganese superoxide dismutase extends islet graft function in a mouse model of autoimmune diabetes. Diabetes 52, 387-393 (2003).
35. Avila J, Barbaro B, Gangemi A et al. Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation. Am. J. Transplant. 5, 2830-2837 (2005).
36. Thomas DA, Stauffer C, Zhao K et al. Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function. J. Am. Soc. Nephrol. 18, 213-222 (2007).
37. Avila JG, Wang Y, Barbaro B et al. Improved outcomes in islet isolation and transplantation by the use of a novel hemoglobin-based O2 carrier. Am. J. Transplant. 6, 2861-2870 (2006).
38. Moberg L, Olsson A, Berne C et al. Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation. Transplantation 76, 1285-1288 (2003).
39. Moberg L, Johansson H, Lukinius A et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 360, 2039-2045 (2002).
40. Johansson H, Lukinius A, Moberg L et al. Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes 54, 1755-1762 (2005).
41. Nilsson B, Berne C, Korsgren O. The recent finding that tissue factor is produced by the pancreatic islets constitutes a possible link between insulin resistance and cardiovascular disease. Am. J. Ther. 12, 551-554 (2005).
42. Moberg L, Korsgren O, Nilsson B. Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABOcompatible blood. Clin. Exp. Immunol. 142, 125-131 (2005).
43. Ehrnfelt C, Kumagai-Braesch M, Uzunel M, Holgersson J. Adult porcine islets produce MCP-1 and recruit human monocytes in vitro. Xenotransplantation 11, 184-194 (2004).
44. Oberholzer J, Yu D, Triponez F et al. Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model. Immunology 97, 173-180 (1999).
45. Badet L, Titus T, Metzen E et al. The interaction between primate blood and mouse islets induces accelerated clotting with islet destruction. Xenotransplantation 9, 91-96 (2002).
46. Kirchhof N, Shibata S, Wijkstrom M et al. Reversal of diabetes in nonimmunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection. Xenotransplantation 11, 396-407 (2004).
47. Tjernberg J, Ekdahl KN, Lambris JD, Korsgren O, Nilsson B. Acute antibodymediated complement activation mediates lysis of pancreatic islets cells and may cause tissue loss in clinical islet transplantation. Transplantation 85, 1193-1199 (2008).
48. Titus TT, Horton PJ, Badet L et al. Adverse outcome of human islet-allogeneic blood interaction. Transplantation 75, 1317-1322 (2003).
49. Schmidt P, Goto M, Le Mauff B, Anegon I, Korsgren O. Adenovirus-mediated expression of human CD55 or CD59 protects adult porcine islets from complement-mediated cell lysis by human serum. Transplantation 75, 697-702 (2003).
50. Fodor WL, Williams BL, Matis LA et al. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proc. Natl Acad. Sci. USA 91, 11153-11157 (1994).
51. Bennet W, Bjorkland A, Sundberg B et al. Expression of complement regulatory proteins on islets of Langerhans: a comparison between human islets and islets isolated from normal and hDAF transgenic pigs. Transplantation 72, 312-319 (2001).
52. Goto M, Johansson H, Maeda A, Elgue G, Korsgren O, Nilsson B. Low-molecular weight dextran sulfate abrogates the instant blood-mediated inflammatory reaction induced by adult porcine islets both in vitro and in vivo. Transplant Proc. 36, 1186-1187 (2004). (Pubitemid 38766317)
53. Wuillemin WA, te Velthuis H, Lubbers YT, de Ruig CP, Eldering E, Hack CE. Potentiation of C1 inhibitor by glycosaminoglycans: dextran sulfate species are effective inhibitors of in vitro complement activation in plasma. J. Immunol. 159, 1953-1960 (1997).
54. Ormsby RJ, Jokiranta TS, Duthy TG et al. Localization of the third heparin-binding site in the human complement regulator factor H1. Mol. Immunol. 43, 1624-1632 (2006).
55. Pangburn MK, Atkinson MA, Meri S. Localization of the heparin-binding site on complement factor H. J. Biol. Chem. 266, 16847-16853 (1991).
56. Laumonier T, Walpen AJ, Maurus CF et al. Dextran sulfate acts as an endothelial cell protectant and inhibits human complement and natural killer cell-mediated cytotoxicity against porcine cells. Transplantation 76, 838-843 (2003).
57. Banz Y, Hess OM, Robson SC et al. Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury. Eur. Heart J. 26, 2334-2343 (2005).
58. Spirig R, van Kooten C, Obregon C, Nicod L, Daha M, Rieben R. The complement inhibitor low molecular weight dextran sulfate prevents TLR4-induced phenotypic and functional maturation of human dendritic cells. J. Immunol. 181, 878-890 (2008).
59. Schmidt P, Magnusson C, Lundgren T, Korsgren O, Nilsson B. Low molecular weight dextran sulfate is well tolerated in humans and increases endogenous expression of islet protective hepatocyte growth factor. Transplantation 86, 1523-1530 (2008).
60. Johansson H, Goto M, Dufrane D et al. Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation. Am. J. Transplant. 6, 305-312 (2006).
61. Spirig R, Gajanayake T, Korsgren O, Nilsson B, Rieben R. Low molecular weight dextran sulfate as complement inhibitor and cytoprotectant in solid organ and islet transplantation. Mol. Immunol. 45, 4084-4094 (2008).
62. Takahashi H, Goto M, Ogawa N et al. Superiority of fresh islets compared with cultured islets. Transplant Proc. 41, 350-351 (2009).
63. Takahashi H, Goto M, Ogawa N et al. Influence of a current style of culture on the quality of isolated pancreatic islets. Transplant Proc. 40, 358-359 (2008).
64. Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B. Inhibition of thrombin abrogates the instant bloodmediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes 51, 1779-1784 (2002).
65. Testa L, Bhindi R, Agostoni P, Abbate A, Zoccai GG, van Gaal WJ. The direct thrombin inhibitor ximelagatran/ melagatran: a systematic review on clinical applications and an evidence based assessment of risk benefit profile. Expert Opin. Drug. Saf. 6, 397-406 (2007).
66. Contreras JL, Eckstein C, Smyth CA et al. Activated protein C preserves functional islet mass after intraportal transplantation: a novel link between endothelial cell activation, thrombosis, inflammation, and islet cell death. Diabetes 53, 2804-2814 (2004).
67. Cui W, Wilson JT, Wen J et al. Thrombomodulin improves early outcomes after intraportal islet transplantation. Am. J. Transplant. 9, 1308-1316 (2009).
68. Cabric S, Sanchez J, Lundgren T et al. Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation. Diabetes 56, 2008-2015 (2007).
69. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat. Med. 9, 669-676 (2003).
70. Schlessinger J, Plotnikov AN, Ibrahimi OA et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol. Cell. 6, 743-750 (2000).
71. Cabric S, Elgue G, Nilsson B, Korsgren O, Schmidt P. Adenovirus-mediated expression of the anticoagulant hirudin in human islets: a tool to make the islets biocompatible to blood. Cell. Transplant. 15, 759-767 (2006).
72. Dwyer KM, Mysore TB, Crikis S et al. The transgenic expression of human CD39 on murine islets inhibits clotting of human blood. Transplantation 82, 428-432 (2006).
73. Ueki M, Yasunami Y, Arima T, Motoyama K, Ikeda S, Tanaka M. Protection of intrahepatic islet grafts from hyperglycemic toxicity by nicotinamide treatment. Transplant Proc. 27, 618 (1995).
74. Jung DY, Park JB, Joo SY et al. Effect of nicotinamide on early graft failure following intraportal islet transplantation. Exp. Mol. Med. 41(11), 782-792 (2009).
75. Ichii H, Wang X, Messinger S et al. Improved human islet isolation using nicotinamide. Am. J. Transplant. 6, 2060-2068 (2006).
76. Vaca P, Berna G, Martin F, Soria B. Nicotinamide induces both proliferation and differentiation of embryonic stem cells into insulin-producing cells. Transplant Proc. 35, 2021-2023 (2003).
77. Vaca P, Berna G, Araujo R et al. Nicotinamide induces differentiation of embryonic stem cells into insulinsecreting cells. Exp. Cell Res. 314, 969-974 (2008).
78. Johansson U, Elgue G, Nilsson B, Korsgren O. Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation. Am. J. Transplant. 5, 2632-2639 (2005).
79. Toso C, Serre-Beinier V, Emamaullee J et al. The role of macrophage migration inhibitory factor in mouse islet transplantation. Transplantation 86, 1361-1369 (2008).
80. Nitta T, Itoh T, Matsuoka N et al. Prevention of early loss of transplanted islets in the liver of mice by adenosine. Transplantation 88, 49-56 (2009).
81. Connolly JE. Pancreatic whole organ transplantation. Surg. Clin. North Am. 58, 383-390 (1978).
82. Brooks-Worrell BM, Peterson KP, Peterson CM, Palmer JP, Jovanovic L. Reactivation of Type 1 diabetes in patients receiving human fetal pancreatic tissue transplants without immunosuppression. Transplantation 69, 1824-1829 (2000). (Pubitemid 30340341)
83. Stegall MD, Loberman Z, Ostrowska A, Coulombe M, Gill RG. Autoimmune destruction of islet grafts in the NOD mouse is resistant to 15-deoxyspergualin but sensitive to anti-CD4 antibody. J. Surg. Res. 64, 156-160 (1996).
84. Okitsu T, Bartlett ST, Hadley GA, Drachenberg CB, Farney AC. Recurrent autoimmunity accelerates destruction of minor and major histoincompatible islet grafts in nonobese diabetic (NOD) mice. Am. J. Transplant. 1, 138-145 (2001).
85. Makhlouf L, Kishimoto K, Smith RN et al. The role of autoimmunity in islet allograft destruction: major histocompatibility complex class II matching is necessary for autoimmune destruction of allogeneic islet transplants after T-cell costimulatory blockade. Diabetes 51, 3202-3210 (2002).
86. Gunnarsson R, Bottazzo GF, Freedman ZR, Lernmark A, Zuhlke H, Groth CG. Allogeneic rejection or recurrence of autoimmunity as the cause of immune destruction of pancreatic grafts. Transplant Proc. 12, 112-113 (1980).
87. Tyden G, Reinholt FP, Sundkvist G, Bolinder J. Recurrence of autoimmune diabetes mellitus in recipients of cadaveric pancreatic grafts. N. Engl. J. Med. 335, 860-863 (1996).
88. Martin-Pagola A, Sisino G, Allende G et al. Insulin protein and proliferation in ductal cells in the transplanted pancreas of patients with Type 1 diabetes and recurrence of autoimmunity. Diabetologia 51, 1803-1813 (2008).
89. Laughlin E, Burke G, Pugliese A, Falk B, Nepom G. Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation. Clin. Immunol. 128, 23-30 (2008).
90. Santamaria P, Nakhleh RE, Sutherland DE, Barbosa JJ. Characterization of T lymphocytes infiltrating human pancreas allograft affected by isletitis and recurrent diabetes. Diabetes 41, 53-61 (1992).
91. Roep BO, Stobbe I, Duinkerken G et al. Auto- and alloimmune reactivity to human islet allografts transplanted into Type 1 diabetic patients. Diabetes 48, 484-490 (1999).
92. Sibley RK, Sutherland DE, Goetz F, Michael AF. Recurrent diabetes mellitus in the pancreas iso- and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab. Invest. 53, 132-144 (1985).
93. Stegall MD, Lafferty KJ, Kam I, Gill RG. Evidence of recurrent autoimmunity in human allogeneic islet transplantation. Transplantation 61, 1272-1274 (1996).
94. Jaeger C, Hering BJ, Hatziagelaki E, Federlin K, Bretzel RG. Glutamic acid decarboxylase antibodies are more frequent than islet cell antibodies in islet transplanted IDDM patients and persist or occur despite immunosuppression. J. Mol. Med. 77, 45-48 (1999).
95. Vantyghem MC, Fajardy I, Pigny P et al. Kinetics of diabetes-associated autoantibodies after sequential intraportal islet allograft associated with kidney transplantation in Type 1 diabetes. Diabetes Metab. 29, 595-601 (2003).
96. Bosi E, Braghi S, Maffi P et al. Autoantibody response to islet transplantation in Type 1 diabetes. Diabetes 50, 2464-2471 (2001). (Pubitemid 33642763)
97. Makhlouf L, Yamada A, Ito T et al. Allorecognition and effector pathways of islet allograft rejection in normal versus nonobese diabetic mice. J. Am. Soc. Nephrol. 14, 2168-2175 (2003).
98. Woehrle M, Markmann JF, Silvers WK, Barker CF, Naji A. Transplantation of cultured pancreatic islets to BB rats. Surgery 100, 334-341 (1986).
99. Markmann JF, Posselt AM, Bassiri H et al. Major-histocompatibility- complex restricted and nonrestricted autoimmune effector mechanisms in BB rats. Transplantation 52, 662-667 (1991).
100. Molano RD, Pileggi A, Berney T et al. Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and antiinterleukin-2 antibody. Transplantation 75, 1812-1819 (2003).
101. Fu F, Hu S, Deleo J et al. Long-term islet graft survival in streptozotocin- and autoimmune-induced diabetes models by immunosuppressive and potential insulinotropic agent FTY720. Transplantation 73, 1425-1430 (2002).
102. Kuttler B, Rosing K, Lehmann M, Brock J, Hahn HJ. Prevention of autoimmune but not allogeneic destruction of grafted islets by different therapeutic strategies. J. Mol. Med. 77, 226-229 (1999).
103. Makhlouf L, Grey ST, Dong V et al. Depleting anti-CD4 monoclonal antibody cures new-onset diabetes, prevents recurrent autoimmune diabetes, and delays allograft rejection in nonobese diabetic mice. Transplantation 77, 990-997 (2004).
104. Guo Z, Wu T, Kirchhof N et al. Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. Transplantation 71, 1656-1665 (2001).
105. Drage M, Zaccone P, Phillips JM et al. Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice. Transplantation 74, 611-619 (2002).
106. Suarez-Pinzon WL, Rabinovitch A. Combination therapy with epidermal growth factor and gastrin delays autoimmune diabetes recurrence in nonobese diabetic mice transplanted with syngeneic islets. Transplant Proc. 40, 529-532 (2008).
107. Bartlett ST, Schweitzer EJ, Kuo PC, Johnson LB, Delatorre A, Hadley GA. Prevention of autoimmune islet allograft destruction by engraftment of donor T cells. Transplantation 63, 299-303 (1997).
108. Georgiou HM, Constantinou D, Mandel TE. Prevention of autoimmunity in nonobese diabetic (NOD) mice by neonatal transfer of allogeneic thymic macrophages. Autoimmunity 21, 89-97 (1995).
109. Li H, Kaufman CL, Ildstad ST. Allogeneic chimerism induces donor-specific tolerance to simultaneous islet allografts in nonobese diabetic mice. Surgery 118, 192-197; discussion 7-8 (1995).
110. Seung E, Iwakoshi N, Woda BA et al. Allogeneic hematopoietic chimerism in mice treated with sublethal myeloablation and anti-CD154 antibody: absence of graft-versus-host disease, induction of skin allograft tolerance, and prevention of recurrent autoimmunity in islet-allografted NOD/Lt mice. Blood 95, 2175-2182 (2000).
111. Nikolic B, Takeuchi Y, Leykin I, Fudaba Y, Smith RN, Sykes M. Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity. Diabetes 53, 376-383 (2004).
112. Scandling JD, Busque S, Dejbakhsh-Jones S et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N. Engl. J. Med. 358, 362-368 (2008).
113. Kawai T, Cosimi AB, Spitzer TR et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N. Engl. J. Med. 358, 353-361 (2008).
114. Wang T, Singh B, Warnock GL, Rajotte RV. Prevention of recurrence of IDDM in islet-transplanted diabetic NOD mice by adjuvant immunotherapy. Diabetes 41, 114-117 (1992).
115. Qu P, Ji RC, Shimoda H, Miura M, Kato S. Study on pancreatic lymphatics in nonobese diabetic mouse with prevention of insulitis and diabetes by adjuvant immunotherapy. Anat. Rec. A. Discov. Mol. Cell. Evol. Biol. 281, 1326-1336 (2004).
116. Lakey JR, Singh B, Warnock GL, Rajotte RV. BCG immunotherapy prevents recurrence of diabetes in islet grafts transplanted into spontaneously diabetic NOD mice. Transplantation 57, 1213-1217 (1994). (Pubitemid 24139644)
117. Casteels K, Waer M, Laureys J et al. Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously diabetic nonobese diabetic mice by a combination of a vitamin D3 analog and cyclosporine. Transplantation 65, 1225-1232 (1998).
118. Orive G, Hernandez RM, Rodriguez Gascon A et al. History, challenges and perspectives of cell microencapsulation. Trends Biotechnol. 22, 87-92 (2004).
119. Chick WL, Like AA, Lauris V. b cell culture on synthetic capillaries: an artificial endocrine pancreas. Science 187, 847-849 (1975).
120. Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science 210, 908-910 (1980).
121. Canaple L, Rehor A, Hunkeler D. Improving cell encapsulation through size control. J. Biomater. Sci. Polym. Ed. 13, 783-796 (2002).
122. Campos-Lisboa AC, Mares-Guia TR, Grazioli G, Goldberg AC, Sogayar MC. Biodritin microencapsulated human islets of Langerhans and their potential for Type 1 diabetes mellitus therapy. Transplant Proc. 40, 433-435 (2008).
123. Kobayashi T, Aomatsu Y, Iwata H et al. Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression. Transplantation 75, 619-625 (2003).
124. Dufrane D, Goebbels RM, Saliez A, Guiot Y, Gianello P. Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: proof of concept. Transplantation 81, 1345-1353 (2006).
125. Duvivier-Kali VF, Omer A, Lopez-Avalos MD, O'Neil JJ, Weir GC. Survival of microencapsulated adult pig islets in mice in spite of an antibody response. Am. J. Transplant. 4, 1991-2000 (2004).
126. Tuch BE, Keogh GW, Williams LJ et al. Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 32(10), 1887-1889 (2009).
127. Mallett AG, Korbutt GS. Alginate modification improves long-term survival and function of transplanted encapsulated islets. Tissue Eng. Part A. 15, 1301-1309 (2009).
128. Barnett BP, Arepally A, Karmarkar PV et al. Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat. Med. 13, 986-991 (2007).
129. Kaufman DB, Morel P, Condie R et al. Beneficial and detrimental effects of RBC-adsorbed antilymphocyte globulin and prednisone on purified canine islet autograft and allograft function. Transplantation 51, 37-42 (1991).
130. Gangemi A, Salehi P, Hatipoglu B et al. Islet transplantation for brittle Type 1 diabetes: the UIC protocol. Am. J. Transplant. 8, 1250-1261 (2008).
131. Froud T, Faradji RN, Pileggi A et al. The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects. Transplantation 86, 36-45 (2008).
132. Froud T, Baidal DA, Faradji R et al. Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes. Transplantation 86, 1695-1701 (2008).
133. Bellin MD, Kandaswamy R, Parkey J et al. Prolonged insulin independence after islet allotransplants in recipients with Type 1 diabetes. Am. J. Transplant. 8, 2463-2470 (2008).
134. Fowler M, Virostko J, Chen Z et al. Assessment of pancreatic islet mass after islet transplantation using in vivo bioluminescence imaging. Transplantation 79, 768-776 (2005).
135. Lu Y, Dang H, Middleton B et al. Bioluminescent monitoring of islet graft survival after transplantation. Mol. Ther. 9, 428-435 (2004).
136. Virostko J, Chen Z, Fowler M, Poffenberger G, Powers AC, Jansen ED. Factors influencing quantification of in vivo bioluminescence imaging: application to assessment of pancreatic islet transplants. Mol. Imaging 3, 333-342 (2004).
137. Kim SJ, Doudet DJ, Studenov AR et al. Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat. Med. 12, 1423-1428 (2006).
138. Toso C, Zaidi H, Morel P et al. Assessment of 18F-FDG-leukocyte imaging to monitor rejection after pancreatic islet transplantation. Transplant Proc. 38, 3033-3034 (2006).
139. Eich T, Eriksson O, Sundin A et al. Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model. Transplantation 84, 893-898 (2007).
140. Evgenov NV, Pratt J, Pantazopoulos P, Moore A. Effects of glucose toxicity and islet purity on in vivo magnetic resonance imaging of transplanted pancreatic islets. Transplantation 85, 1091-1098 (2008).
141. Hathout E, Sowers L, Wang R et al. In vivo magnetic resonance imaging of vascularization in islet transplantation. Transpl. Int. 20, 1059-1065 (2007).
142. Medarova Z, Moore A. Non-invasive detection of transplanted pancreatic islets. Diabetes Obes. Metab. 10(Suppl. 4), 88-97 (2008).
143. Frank A, Deng S, Huang X et al. Transplantation for Type I diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann. Surg. 240, 631-640; discussion 640-643 (2004).
144. Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin. Transpl. 19, 433-455 (2005).
145. Sollinger HW, Vernon WB, D'Alessandro AM, Kalayoglu M, Stratta RJ, Belzer FO. Combined liver and pancreas procurement with Belzer-UW solution. Surgery 106, 685-690; discussion 690-691 (1989).
146. Lakey JR, Tsujimura T, Shapiro AM, Kuroda Y. Preservation of the human pancreas before islet isolation using a two-layer (UW solution- perfluorochemical) cold storage method. Transplantation 74, 1809-1811 (2002). (Pubitemid 36019343)
147. Lakey JR, Helms LM, Kin T et al. Serine-protease inhibition during islet isolation increases islet yield from human pancreases with prolonged ischemia. Transplantation 72, 565-570 (2001).
148. Bucher P, Mathe Z, Morel P et al. Assessment of a novel two-component enzyme preparation for human islet isolation and transplantation. Transplantation 79, 91-97 (2005).
149. Bucher P, Mathe Z, Bosco D et al. Serva collagenase NB1: a new enzyme preparation for human islet isolation. Transplant Proc. 36, 1143-1144 (2004).
150. Quan N, Ho E, La W, Tsai YH, Bray T. Administration of NF-kB decoy inhibits pancreatic activation of NF-kB and prevents diabetogenesis by alloxan in mice. FASEB J. 15, 1616-1618 (2001).
151. Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL, Tiedge M. Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-kB activation in insulin-producing cells. Diabetes 52, 93-101 (2003).
152. Barshes NR, Wyllie S, Goss JA. Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J. Leukoc. Biol. 77, 587-597 (2005).
153. Olsson R, Carlsson PO. Better vascular engraftment and function in pancreatic islets transplanted without prior culture. Diabetologia 48, 469-476 (2005).
154. Olsson R, Maxhuni A, Carlsson PO. Revascularization of transplanted pancreatic islets following culture with stimulators of angiogenesis. Transplantation 82, 340-347 (2006).
155. Johansson A, Sandvik D, Carlsson PO. Inhibition of p38 MAP kinase in the early posttransplantation phase redistributes blood vessels from the surrounding stroma into the transplanted endocrine tissue. Cell. Transplant. 15, 483-488 (2006).
156. Markmann JF, Jacobson J, Kimura H, Brayman KL, Barker CF, Naji A. Prevention of autoimmune damage to islet grafts in BB rats by antibody therapy. Transplant Proc. 21, 2703-2704 (1989).
157. Maki T, Ichikawa T, Blanco R, Porter J. Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum. Proc. Natl Acad. Sci. USA 89, 3434-3438 (1992).
158. Kover KL, Geng Z, Hess D, Benjamin C, Moore WV. CD40/154 blockade and rejection of islet allografts in the streptozotocin and autoimmune diabetic rat. Pediatr. Diabetes 2, 178-183 (2001).
159. Molano RD, Pileggi A, Berney T et al. Prolonged islet allograft survival in diabetic NOD mice by targeting CD45RB and CD154. Diabetes 52, 957-964 (2003).
160. Posselt AM, Naji A, Roark JH, Markmann JF, Barker CF. Intrathymic islet transplantation in the spontaneously diabetic BB rat. Ann. Surg. 214, 363-371; discussion 71-73 (1991).
161. Wang H, Lee SS, Gao W et al. Donor treatment with carbon monoxide can yield islet allograft survival and tolerance. Diabetes 54, 1400-1406 (2005).
162. Wang H, Lee SS, Dell'Agnello C et al. Bilirubin can induce tolerance to islet allografts. Endocrinology 147, 762-768 (2006).
163. Sakuma Y, Ricordi C, Miki A et al. Effect of pituitary adenylate cyclase-activating polypeptide in islet transplantation. Transplant Proc. 41, 343-345 (2009).
164. Hiramatsu S, Hoog A, Moller C, Grill V. Treatment with diazoxide causes prolonged improvement of b-cell function in rat islets transplanted to a diabetic environment. Metabolism 49, 657-661 (2000).
165. Wang X, Alfrey EJ, Posselt A, Tafra L, Alak AM, Dafoe DC. Intraportal delivery of immunosuppression to intrahepatic islet allograft recipients. Transpl. Int. 8, 268-272 (1995).
166. Arita S, Kasraie A, Une S, Ohtsuka S, Smith CV, Mullen Y. Prolongation of islet allograft survival in mice by combined treatment with pravastatin and low-dose cyclosporine. Cell. Transplant. 10, 639-644 (2001).
167. Farkas G, Szasz Z, Lazar G Jr, Csanadi J, Lazar G. Macrophage blockade induced by repeated gadolinium chloride injections saves human fetal islet xenografting in rats. Transplant Proc. 34, 1460-1461 (2002).