Clinical islet transplant: Current and future directions towards tolerance

Immunological Reviews

Volumn 196, Issue , 2003, Pages 219-236

  Shapiro, A M James ^a   Nanji, Sulaiman ^a   Lakey, Jonathan R T ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

15 DEOXYSPERGUALIN; BELATACEPT; CD4 ANTIGEN; CD40 LIGAND MONOCLONAL ANTIBODY; COLECALCIFEROL; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACLIZUMAB; ETANERCEPT; FAS LIGAND; HU 5C 8; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 2 RECEPTOR; LAZAROID; NICOTINAMIDE; PENTOXIFYLLINE; PRAVASTATIN; RAPAMYCIN; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ALLOTYPE SUPPRESSION; ANEMIA; AUTOIMMUNITY; CHIMERA; CHOLESTEROL BLOOD LEVEL; CHRONIC GRAFT REJECTION; CLINICAL PROTOCOL; DIABETOGENESIS; GRAFT REJECTION; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HUMAN; HYPERTENSION; HYPOGLYCEMIA; INSULIN DEPENDENCE; KIDNEY ALLOGRAFT; KIDNEY DISEASE; KIDNEY GRAFT; LIVER GRAFT; LOW DRUG DOSE; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DEPLETION; MOUTH ULCER; PANCREAS ISLET TRANSPLANTATION; PRIORITY JOURNAL; REVIEW; TRANSPLANTATION TOLERANCE; WEIGHT REDUCTION; WHOLE BODY RADIATION; XENOGRAFT;

ANIMALS; HUMANS; ISLETS OF LANGERHANS; ISLETS OF LANGERHANS TRANSPLANTATION; TRANSPLANTATION; TRANSPLANTATION TOLERANCE;

EID: 0344984343     PISSN: 01052896     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1600-065X.2003.00085.x     Document Type: Review

References (221)

1. Boyle JP, et al. Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U. S. Diabetes Care 2001;24:1936-1940.
2. Skyler JS, Oddo C. Diabetes trends in the USA. Diabetes Metab Res Rev 2002;18: S21-S26.
3. Keen H. The Diabetes Control Complications Trial (DCCT). Health Trends 1994;26: 41-43.
4. Diabetes Control and Complications Trial (DCCT). DCCT Res Group. Update. Diabetes Care 1990;13:427-433.
5. Adverse Events and Their Association with Treatment Regimens in the Diabetes Control and Complications Trial. Diabetes Care 1995;18:1415-1427.
6. Tyden G, Tollemar J, Bolinder J. Combined pancreas and kidney transplantation improves survival in patients with end-stage diabetic nephropathy. Clin Transplant 2000;14: 505-508.
7. Reddy KS, et al. Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure. Am J Kidney Dis 2003;41: 464-470.
8. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998;339:69-75.
9. Secchi A, et al. Effect of pancreas transplantation on life expectancy, kidney function and quality of life in uraemic type 1 (insulin-dependent) diabetic patients. Diabetologia 1991;34:S141-S144.
10. Gross CR, Limwattananon C, Matthees BJ. Quality of life after pancreas transplantation: a review. Clin Transplant 1998;12:351-361.
11. Brendel M, Hering B, Schulz A, Bretzel R. International Islet Transplant Registry Report. Germany: University of Giessen 2001, Report No.: Newsletter No. 8.
12. Hering B, Ricordi C. Islet transplantation for patients with Type 1 diabetes: results, research priorities, and reasons for optimism. Graft 1999;2:12-27.
13. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes 1988;37: 413-420.
14. Lakey JR, et al. Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion. Cell Transplant 1999;8:285-292.
15. Linetsky E, Bottino R, Lehmann R, Alejandro R, Inverardi L, Ricordi C. Improved human islet isolation using a new enzyme blend, liberase. Diabetes 1997;46:1120-1123.
16. Robertson GS, Chadwick DR, Contractor H, James RF, London NJ. The optimization of large-scale density gradient isolation of human islets. Acta Diabetol 1993;30:93-98.
17. Bretzel RG, et al. Islet transplantation: present clinical situation and future aspects. Exp Clin Endocrinol Diabetes 2001;109:S384-S399.
18. Secchi A, et al. Insulin secretory patterns and blood glucose homeostasis after islet allotransplantation in IDDM patients: comparison with segmental-or whole-pancreas transplanted patients through a long term longitudinal study. J Mol Med 1999;77:133-139.
19. Shapiro AM, 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.
20. Hering B, et al. Successful single donor islet transplantation in type 1 diabetes. Am J Transplant 2003;3:296.
21. Goss JA, et al. Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center. Transplantation 2002;74:1761-1766.
22. Fraker CA, Alejandro R, Ricordi C. Use of oxygenated perfluorocarbon toward making every pancreas count. Transplantation 2002;74:1811-1812.
23. Markmann JF, et al. The use of non-heart-beating donors for isolated pancreatic islet transplantation. Transplantation 2003;75:1423-1429.
24. Andersson A, Hellerstrom C. Isolated pancreatic islets in tissue culture: an investigative tool for studies of islet metabolism and hormone production. In: von Wasielewski E, Chick WL, eds. Pancreatic Beta Cell Culture, Amsterdam: Excerpta Medica 1977:55-63.
25. Lazarow A, Wells LJ, Carpenter AM, Hegre OD, Leonard RJ, McEvoy RC. The Banting memorial lecture 1973: islet differentiation, organ culture, and transplantation. Diabetes 1973;22:877-912.
26. Rajotte RV, Evans MG, Warnock GL, Kneteman NM. Islet cryopreservation. Horm Metab Res Suppl 1990;25:72-81.
27. Williams P. Notes on diabetes treated with extract and by grafts of sheep's pancreas. Br Med J 1894;2:1303-1304.
28. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 1967;61: 827-837.
29. Sutherland DE, et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 2001;233: 463-501.
30. Bartlett ST, et al. Equivalent success of simultaneous pancreas kidney and solitary pancreas transplantation. A prospective trial of tacrolimus immunosuppression with percutaneous biopsy. Ann Surg 1996;224:440-449: discussion 449-452.
31. Odorico JS, et al. Improved solitary pancreas transplant graft survival in the modern immunosuppressive era. Cell Transplant 2000;9:919-927.
32. Philosophe B, et al. Superiority of portal venous drainage over systemic venous drainage in pancreas transplantation: a retrospective study. Ann Surg 2001;234:689-696.
33. Gruessner RW, Sutherland DE, Najarian JS, Dunn DL, Gruessner AC. Solitary pancreas transplantation for nonuremic patients with labile insulin-dependent diabetes mellitus. Transplantation 1997;64:1572-1577.
34. Kendall DM, Rooney DP, Smets YF, Salazar Bolding L, Robertson RP. Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy. Diabetes 1997;46:249-257.
35. Luzi L. Pancreas transplantation and diabetic complications. N Engl J Med 1998;339: 115-117.
36. Tyden G, Bolinder J, Solders G, Brattstrom C, Tibell A, Groth CG. Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation. Transplantation 1999;67:645-648.
37. Ballinger W, Lacy P. Transplantation of intact pancreatic islets in rats. Surgery 1972;72:175-186.
38. Kemp C, Knight M, Scharp D, Ballinger W, Lacy P. Effect of transplantation site on the result of pancreatic islet isografts in diabetic rats. Diabetologia 1973;9:486-491.
39. Lacy P, Kostianovsky M. Method for the isolation of intact islets of Langerhans' from the rat pancreas. Diabetes 1967;16:35-39.
40. Younoszai R, Sorensen R, Lindall A. Homotransplantation of isolated pancreatic islets. Diabetes 1970;19:406-407.
41. Reckard CR, Ziegler MM, Barker CF. Physiological and immunological consequences of transplanting isolated pancreatic islets. Surgery 1973;74:91-99.
42. Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC. Human islet transplantation: a preliminary report. Transplant Proc 1977;9:233-236.
43. Largiader F, Kolb E, Binswanger U, Illig R. Successful allotransplantation of an island of Langerhans'. Schweiz Med Wochenschr 1979;109:1733-1736.
44. Tzakis AG, et al. Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet 1990;336:402-405.
45. Ricordi C, et al. Human islet isolation and allotransplantation in 22 consecutive cases. Transplantation 1992;53:407-414.
46. Brendel M, Hering B, Schulz A, Bretzel R. International Islet Transplant Registry Report. Germany: University of Giessen 1999, Report No.: Newsletter No. 8.
47. Boker A, Rothenberg L, Hernandez C, Kenyon NS, Ricordi C, Alejandro R. Human islet transplantation: update. World J Surg 2001;25:481-486.
48. Bretzel RG, et al. Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management. J Mol Med 1999;77:140-143.
49. Maffi P, et al. Per and peri-operative management influences the clinical outcome of islet transplantation. Am J Transplant 2001;1:181.
50. Sutherland DE, et al. Twin-to-twin pancreas transplantation: reversal and reenactment of the pathogenesis of type I diabetes. Trans Assoc Am Physicians 1984;97:80-87.
51. 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 1985;53:132-144.
52. Vu MD, et al. Tacrolimus (FK506) and sirolimus (rapamycin) in combination are not antagonistic but produce extended graft survival in cardiac transplantation in the rat. Transplantation 1997;64:1853-1856.
53. Qi S, et al. Effect of tacrolimus (FK506) and sirolimus (rapamycin) mono-and combination therapy in prolongation of renal allograft survival in the monkey. Transplantation 2000;69:1275-1283.
54. McAlister VC, Gao Z, Peltekian K, Domingues J, Mahalati K, MacDonald AS. Sirolimus-tacrolimus combination immunosuppression. Lancet 2000;355:376-377.
55. Shapiro AM, Suarez-Pinzon WL, Power R, Rabinovitch A. Combination therapy with low dose sirolimus and tacrolimus is synergistic in preventing spontaneous and recurrent autoimmune diabetes in non-obese diabetic mice. Diabetologia 2002;45:224-230.
56. Ryan EA, et al. Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 2002;51: 2148-2157.
57. Shapiro A, et al. Three year follow-up in clinical islet-alone transplant with the Edmonton Protocol, and preliminary impact of infliximab and Campath-1H. Am J Transplant 2003;3:296.
58. Shapiro A, et al. International multicenter trial of islet transplantation using the Edmonton Protocol in patients with type 1 diabetes. Am J Transplant 2003;3:152.
59. Matsumoto S, Rigley TH, Qualley SA, Kuroda Y, Reems JA, Stevens RB. Efficacy of the oxygen-charged static two-layer method for short-term pancreas preservation and islet isolation from nonhuman primate and human pancreata. Cell Transplant 2002;11:769-777.
60. Matsumoto S, Kuroda Y. Perfluorocarbon for organ preservation before transplantation. Transplantation 2002;74:1804-1809.
61. Tanioka Y, et al. Effect of pancreatic warm ischemia on islet yield and viability in dogs. Transplantation 1997;64:1637-1641.
62. Tsujimura T, et al. Human islet transplantation from pancreases with prolonged cold ischemia using additional preservation by the two-layer (UW solution/ perfluorochemical) cold-storage method. Transplantation 2002;74:1687-1691.
63. 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 2002;74: 1809-1811.
64. Hering BJ, et al. Impact of two-layer pancreas preservation on islet isolation and transplantation. Transplantation 2002;74:1813-1816.
65. Ricordi C, 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.
66. Kaufman DB, Baker MS, Chen X, Leventhal JR, Stuart FP. Sequential kidney/islet transplantation using prednisone-free immunosuppression. Am J Transplant 2002;2:674-677.
67. Herold KC, Burton JB, Francois F, Poumian-Ruiz E, Glandt M, Bluestone JA. Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3gamma1 (Ala-Ala). J Clin Invest 2003;111:409-418.
68. Chatenoud L, Primo J, Bach JF. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol 1997;158:2947-2954.
69. Herold KC, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002;346: 1692-1698.
70. Casey JJ, et al. Portal venous pressure changes after sequential clinical islet transplantation. Transplantation 2002;74:913-915.
71. Ricordi C, Finke EH, Lacy PE. A method for the mass isolation of islets from the adult pig pancreas. Diabetes 1986;35:649-653.
72. Ricordi C, Lacy PE, Scharp DW. Automated islet isolation from human pancreas. Diabetes 1989;38:140-142.
73. Lakey JR, Cavanagh TJ, Zieger MA, Wright M. Evaluation of a purified enzyme blend for the recovery and function of canine pancreatic islets. Cell Transplant 1998;7: 365-372.
74. Lake SP, et al. Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator. Diabetes 1989;38:143-145.
75. Ricordi C, Lakey JR, Hering BJ. Challenges toward standardization of islet isolation technology. Transplant Proc 2001;33:1709.
76. Brandhorst H, et al. Successful human islet isolation utilizing recombinant collagenase. Diabetes 2003;52:1143-1146.
77. Hesse F, Burtscher H, Popp F, Ambrosius D. Recombinant enzymes for islet isolation: purification of a collagenase from Clostridium histolyticum and cloning/ expression of the gene. Transplant Proc 1995;27:3287-3289.
78. Gaber AO, Fraga DW, Callicutt CS, Gerling IC, Sabek OM, Kotb MY. Improved in vivo pancreatic islet function after prolonged in vitro islet culture. Transplantation 2001;72:1730-1736.
79. Fraga DW, Sabek O, Hathaway DK, Gaber AO. A comparison of media supplement methods for the extended culture of human islet tissue. Transplantation 1998;65: 1060-1066.
80. Jahr H, Hussmann B, Eckhardt T, Bretzel RG. Successful single donor islet allotransplantation in the streptozotocin diabetes rat model. Cell Transplant 2002;11:513-518.
81. Beattie GM, et al. A novel approach to increase human islet cell mass while preserving beta-cell function. Diabetes 2002;51:3435-3439.
82. Garda-Ocana A, Vasavada RC, Takane KK, Cebrian A, Lopez-Talavera JC, Stewart AF. Using beta-cell growth factors to enhance human pancreatic Islet transplantation. J Clin Endocrinol Metab 2001;86:984-988.
83. Vinik A, Rafaeloff R, Pittenger G, Rosenberg L, Duguid W. Induction of pancreatic islet neogenesis. Horm Metab Res 1997;29: 278-293.
84. Rosenberg L, Duguid WP, Healy M, Clas D, Vinik AI. Reversal of diabetes by the induction of islet cell neogenesis. Transplant Proc 1992;24:1027-1028.
85. Brand SJ, et al. Pharmacological treatment of chronic diabetes by stimulating pancreatic beta-cell regeneration with systemic co-administration of EGF and gastrin. Pharmacol Toxicol 2002;91:414-420.
86. Faustman DL, Steinman RM, Gebel HM, Hauptfeld V, Davie JM, Lacy PE. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci USA 1984;81:3864-3868.
87. Lacy PE, Finke EH, Janney CG, Davie JM. Prolongation of islet xenograft survival by in vitro culture of rat megaislets in 95% O2. Transplantation 1982;33:588-592.
88. Hardy MA, Lau HT, Weber C, Reemtsma K. Pancreatic islet transplantation: immunoalteration with ultraviolet irradiation. World J Surg 1984;8:207-213.
89. Shapiro J. Eighty years after insulin: parallels with modern islet transplantation. CMAJ 2002;167:1398-1400.
90. Papas KK, et al. NMR spectroscopy in beta cell engineering and islet transplantation. Ann N Y Acad Sci 2001;944:96-119.
91. Thomas F, et al. A tripartite anoikis-like mechanism causes early isolated islet apoptosis. Surgery 2001;130:333-338.
92. Stadlbauer V, Schaffellner S, Iberer F, Lackner C, Leigl B, Zink B, et al. Occurance of apoptosis during ischemia in porcine pancreas islet cells. Int J Artif Organs 2003;26:205-210.
93. Moberg L, et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 2002;360: 2039-2045.
94. 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 2000;105:125-133.
95. Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes 2002;51:1779-1784.
96. Lammert E, et al. Role VEGF-a vascularization pancreatic islets. Curr Biol 2003;13:1070-1074.
97. Watanabe H, et al. Immunohistochemical studies on vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1/CD-31 in islet transplantation. Pancreas 2000;21:165-173.
98. Juang JH, Kuo CH, Hsu BR. Effects of vascular endothelial growth factor on islet isografts. Transplant Proc 2002;34: 2690-2692.
99. Reimer MK, Mokshagundam SP, Wyler K, Sundler F, Ahren B, Stagner JI. Local growth factors are beneficial for the autonomic reinnervation of transplanted islets in rats. Pancreas 2003;26:392-397.
100. Gores PF, Najarian JS, Stephanian E, Lloveras JJ, Kelley SL, Sutherland DE. Insulin independence in type I diabetes after transplantation of unpurified islets from single donor with 15-deoxyspergualin. Lancet 1993;341:19-21.
101. Kaufman DB, et al. Effect of 15-deoxyspergualin on immediate function and long-term survival of transplanted islets in murine recipients of a marginal islet mass. Diabetes 1994;43:778-783.
102. Farney AC, et al. Inhibition of pancreatic islet beta cell function by tumor necrosis factor is blocked by a soluble tumor necrosis factor receptor. Transplant Proc 1993;25:865-866.
103. Brandhorst D, Brandhorst H, Zwolinski A, Nahidi F, Bretzel RG. High-dosed nicotinamide decreases early graft failure after pig to nude rat intraportal islet transplantation. Transplantation 2002;73:74-79.
104. Knip M, et al. Safety of high-dose nicotinamide: a review. Diabetologia 2000;43:1337-1345.
105. Hu Y, et al. Effects of nicotinamide on prevention and treatment of streptozotocin-induced diabetes mellitus in rats. Chin Med J (Engl) 1996;109:819-822.
106. Gysemans C, et al. Treatment of autoimmune diabetes recurrence in non-obese diabetic mice by mouse interferon-beta in combination with an analogue of 1alpha,25-dihydroxyvitamin-D3. Clin Exp Immunol 2002;128:213-220.
107. Riachy R, et al. Beneficial effect of 1,25 dihydroxyvitamin D3 on cytokine-treated human pancreatic islets. J Endocrinol 2001;169:161-168.
108. Casteels K, 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 1998;65:1225-1232.
109. Juang JH, Kuo CH, Hsu BR. Beneficial effects of pentoxiphylline on islet transplantation. Transplant Proc 2000;32:1073-1075.
110. Shapiro AM, Hao E, Rajotte RV, Kneteman NM. Impact of Lazaroid U74006F on ischemia and reperfusion injury of islets after transplantation in the rat. Transplant Proc 1996;28:85-86.
111. Arita S, et al. Prevention of primary nonfunction of canine islet autografts by treatment with pravastatin. Transplantation 2002;73:7-12.
112. Contreras JL, Smyth CA, Bilbao G, Young CJ, Thompson JA, Eckhoff DE. Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Transplantation 2002;74:1063-1069.
113. Buhler LH, et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Transplantation 2002;74:1405-1409.
114. Sykes M, Spitzer TR. Non-myeloblative induction of mixed hematopoietic chimerism: application to transplantation tolerance and hematologic malignancies in experimental and clinical studies. Cancer Treat Res 2002;110:79-99.
115. Spitzer TR, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation 1999;68:480-484.
116. Strober S, Benike C, Krishnaswamy S, Engleman EG, Grumet FC. Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity. Transplantation 2000;69:1549-1554.
117. Manez R, et al. Temporary withdrawal of immunosuppression for life-threatening infections after liver transplantation. Transplantation 1994;57:149-151.
118. Mazariegos GV, Reyes J, Marino I, Flynn B, Fung JJ, Starzl TE. Risks and benefits of weaning immunosuppression in liver transplant recipients: long-term follow-up. Transplant Proc 1997;29:1174-1177.
119. Mazariegos GV, et al. Weaning of immunosuppression in liver transplant recipients. Transplantation 1997;63: 243-249.
120. Starzl TE, Demetris AJ, Murase N, Ildstad S, Ricordi C, Trucco M. Cell migration, chimerism, and graft acceptance. Lancet 1992;339:1579-1582.
121. Starzl TE, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003;361: 1502-1510.
122. Oike F, et al. Complete withdrawal of immunosuppression in living donor liver transplantation. Transplant Proc 2002;34:1521.
123. Tanaka K, Kiuchi T. Living-donor liver transplantation in the new decade: perspective from the twentieth to the twenty-first century. J Hepatobiliary Pancreat Surg 2002;9:218-222.
124. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol 2003;3:199-210.
125. + regulatory T cells that express toll-like receptors. J Exp Med 2003;197:397-401.
126. Madsen JC. Tailoring tolerance to prevent chronic rejection. Transplantation 2001;72:S10-S12.
127. Sayegh MH, Carpenter CB. Tolerance and chronic rejection. Kidney Int Suppl 1997;58:511-514.
128. Selawry HP, Whittington K. Extended allograft survival of islets grafted into intra-abdominally placed testis. Diabetes 1984;33:405-406.
129. Tze WJ, Tai J. Intrathecal allotransplantation of pancreatic endocrine cells in diabetic rats. Transplantation 1986;41:531-534.
130. Posselt AM, Barker CF, Tomaszewski JE, Markmann JF, Choti MA, Naji A. Induction of donor-specific unresponsiveness by intrathymic islet transplantation. Science 1990;249:1293-1295.
131. Takeda Y, et al. Protection of islet allografts transplanted together with Fas ligand expressing testicular allografts. Diabetologia 1998;41:315-321.
132. Korbutt GS, Elliott JF, Rajotte RV. Cotransplantation of allogeneic islets with allogeneic testicular cell aggregates allows long-term graft survival without systemic immunosuppression. Diabetes 1997;46:317-322.
133. Yang H, Wright JR Jr. Co-encapsulation of Sertoli enriched testicular cell fractions further prolongs fish-to-mouse islet xenograft survival. Transplantation 1999;67:815-820.
134. Orive G, et al. Cell encapsulation: promise and progress. Nat Med 2003;9:104-107.
135. Soon-Shiong P, et al. Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets. Transplantation 1992;54:769-774.
136. Soon-Shiong P, et al. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 1994;343:950-951.
137. Sun Y, Ma X, Zhou D, Vacek I, Sun A. Normalization of diabetes in spontaneously diabetic cynomologus monkeys by xenografts of microencapsulated porcine islets without immunosuppression. J Clin Invest 1996;98:1417-1422.
138. Duvivier V, Omer A, Parent R, O'Neil J, Weir G. Long-term survival of islets against auto-and allo-immunity in diabetic NOD mice using non-permselective barium alginate capsules. Am J Transplant 2001;1:370.
139. Pugliese A. Insulin expression in the thymus, tolerance, and type 1 diabetes. Diabetes Metab Rev 1998;14:325-327.
140. Nomura Y, Mullen Y, Stein E. Syngeneic islets transplanted into the thymus of newborn mice prevent diabetes and reduce insulitis in the NOD mouse. Transplant Proc 1993;25:963-964.
141. James T, Jin MX, Chowdhury NC, Oluwole SF. Tolerance induction to rat islet allografts by intrathymic inoculation of donor spleen cells. Transplantation 1993;56: 1148-1152.
142. Chowdhury NC, et al. Comparative studies of specific acquired systemic tolerance induced by intrathymic inoculation of a single synthetic Wistar-Furth (RT1U) allo-MHC class I (RT1.AU) peptide or WAG (RT1U)-derived class I peptide. Transplantation 1998;66:1059-1066.
143. Posselt AM, Odorico JS, Barker CF, Naji A. Promotion of pancreatic islet allograft survival by intrathymic transplantation of bone marrow. Diabetes 1992;41:771-775.
144. Arias-Diaz J, et al. CT-guided fine-needle approach for intrathymic islet transplantation in a diabetic patient. Pancreas 1996;12:100-102.
145. Li H, Inverardi L, Molano RD, Pileggi A, Ricordi C. Nonlethal conditioning for the induction of allogeneic chimerism and tolerance to islet allografts. Transplantation 2003;75:966-970.
146. Starzl TE, Demetris AJ, Murase N, Thomson AW, Trucco M, Ricordi C. Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation. Trends Pharmacol Sci 1993;14:217-223.
147. Starzl TE, Demetris AJ. Transplantation tolerance, microchimerism, and the two-way paradigm. Theor Med Bioeth 1998;19:441-455.
148. Ricordi C, Murase N, Rastellini C, Behboo R, Demetris AJ, Starzl TE. Indefinite survival of rat islet allografts following infusion of donor bone marrow without cytoablation. Cell Transplant 1996;5:53-55.
149. Ciancio G, et al. Donor bone marrow infusion in renal transplantation. Transplant Proc 1998;30:1365-1366.
150. Angelico MC, et al. Transplantation of islets of Langerhans' in patients with insulin-requiring diabetes mellitus undergoing orthotopic liver transplantation - the Miami experience. J Mol Med 1999;77:144-147.
151. Ricordi C, et al. High-dose donor bone marrow infusions to enhance allograft survival: the effect of timing. Transplantation 1997;63:7-11.
152. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 1991;174:561-569.
153. Linsley PS, et al. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 1992;257:792-795.
154. Pearson TC, Alexander DZ, Winn KJ, Linsley PS, Lowry RP, Larsen CP. Transplantation tolerance induced by CTLA4-Ig. Transplantation 1994;57:1701-1706.
155. Jordan SC, Matsumara Y, Zuo XJ, Marchevsky A, Linsley P, Matloff J. Donor-specific transfusions enhance the immunosuppressive effects of single-dose cyclosporine A and CTLA4-Ig but do not result in long-term graft acceptance in a histoincompatible model of rat lung allograft rejection. Transpl Immunol 1996;4:33-37.
156. Bolling SF, Lin H, Wei RQ, Linsley P, Turka LA. The effect of combination cyclosporine and CTLA4-Ig therapy on cardiac allograft survival. J Surg Res 1994;57:60-64.
157. Lin H, et al. Long-term acceptance of major histocompatibility complex mismatched cardiac allografts induced by CTLA4Ig plus donor-specific transfusion. J Exp Med 1993;178:1801-1806.
158. Roy-Chaudhury P, et al. CTLA4Ig attenuates accelerated rejection (presensitization) in the mouse islet allograft model. Transplantation 1997;64:172-175.
159. Lenschow DJ, et al. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig. Science 1992;257:789-792.
160. Weber CJ, et al. CTLA4-Ig prolongs survival of microencapsulated neonatal porcine islet xenografts in diabetic NOD mice. Cell Transplant 1997;6:505-508.
161. Chahine AA, Yu M, McKernan MM, Stoeckert C, Lau HT. Immunomodulation of pancreatic islet allografts in mice with CTLA4Ig secreting muscle cells. Transplantation 1995;59:1313-1318.
162. Gainer AL, et al. Improved survival of biolistically transfected mouse islet allografts expressing CTLA4-Ig or soluble Fas ligand. Transplantation 1998;66:194-199.
163. Levisetti MG, et al. Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol 1997;159:5187-5191.
164. Yang Y, Wilson JM. CD40 ligand-dependent T cell activation, requirement of B7-CD28 signaling through CD40. Science 1996;273:1862-1864.
165. Grewal IS, et al. Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. Science 1996;273:1864-1867.
166. Larsen CP, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996;381:434-438.
167. Zheng XX, et al. CTLA4 Signals are required to optimally induce allograft tolerance with combined donor-specific transfusion and anti-CD 154 monoclonal antibody treatment. J Immunol 1999;162:4983-4990.
168. Kirk AD, et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci USA 1997;94:8789-8794.
169. Kenyon N. Personal communication. 1998.
170. Kenyon NS, et al. Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci USA 1999;96:8132-8137.
171. Kirk AD, et al. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med 1999;5:686-693.
172. Pearson TC, et al. Anti-CD40 therapy extends renal allograft survival in rhesus macaques. Transplantation 2002;74:933-940.
173. Larsen CP, Pearson TC. The CD40 pathway in allograft rejection, acceptance, and tolerance. Curr Opin Immunol 1997;9:641-647.
174. Adams AB, et al. Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Diabetes 2002;51:265-270.
175. Moreland LW, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum 2002;46:1470-1479.
176. Coyle AJ, Gutierrez-Ramos JC. The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T cell function. Nat Immunol 2001;2:203-209.
177. Li Y, Zheng XX, Li XC, Zand MS, Strom TB. Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment. Transplantation 1998;66:1387-1388.
178. Li Y, Li XC, Zheng XX, Wells AD, Turka LA, Strom TB. Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat Med 1999;5:1298-1302.
179. Sharland A, et al. Evidence that apoptosis of activated T cells occurs in spontaneous tolerance of liver allografts and is blocked by manipulations which break tolerance. Transplantation 1999;68:1736-1745.
180. Smiley ST, Csizmadia V, Gao W, Turka LA, Hancock WW. Differential effects of cyclosporine A, methylprednisolone, mycophenolate, and rapamycin on CD154 induction and requirement for NFκB: implications for tolerance induction. Transplantation 2000;70:415-419.
181. Spitzer TR, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation 1999;68:480-484.
182. Seung E, 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 2000;95:2175-2182.
183. Contreras JL, et al. Long-term functional islet mass and metabolic function after xenoislet transplantation in primates. Transplantation 2000;69:195-201.
184. Thomas JM, et al. Peritransplant tolerance induction in macaques: early events reflecting the unique synergy between immunotoxin and deoxyspergualin. Transplantation 1999;68:1660-1673.
185. Thomas JM, et al. Durable donor-specific T and B cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic allograft nephropathy. Transplantation 2000;69:2497-2503.
186. Thomas JM, et al. Successful reversal of streptozotocin-induced diabetes with stable allogeneic islet function in a preclinical model of type 1 diabetes. Diabetes 2001;50:1227-1236.
187. Gruessner RW, Kendall DM, Drangstveit MB, Gruessner AC, Sutherland DE. Simultaneous pancreas-kidney transplantation from live donors. Ann Surg
188. Humar A, Gruessner RW, Sutherland DE. Living related donor pancreas and pancreas-kidney transplantation. Br Med Bull 1997;53:879-891.
189. Sutherland DE, Goetz FC, Najarian JS. Living-related donor segmental pancreatectomy for transplantation. Transplant Proc 1980;12:19-25.
190. Kendall DM, Sutherland DE, Najarian JS, Goetz FC, Robertson RP. Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. N Engl J Med 1990;322:898-903.
191. Griffin SM, Alderson D, Farndon JR. Comparison of harvesting methods for islet transplantation. Br J Surg 1986;73: 712-715.
192. Libman I, Songer T, Laporte R. How many people in the U.S. have IDDM? Diabetes Care 1993;16:841-842.
193. Amos A, McCarty D, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med 1997;14:S1-S85.
194. Harper AM, Rosendale JD. The UNOS OPTN waiting list and donor registry: 1988-1996. Clin Transpl 1996, 69-90.
195. Report of the Canadian Organ Replacement Registry. 1998.
196. Marx JL. Cloning sheep and cattle embryos. Science 1988;239:463-464.
197. Blacksher E. Cloning human beings. Responding to the National Bioethics Advisory Commission's report. Hastings Cent Rep 1997;27:6-9.
198. Schramm FR. The Dolly case, the Polly drug, and the morality of human cloning. Cad Saude Publica 1999;15:51-64.
199. Wood PG. To what extent can the law control human cloning? Med Sci Law 1999;39:5-10.
200. Bonner-Weir S, et al. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci USA 2000;97: 7999-8004.
201. Rafaeloff R, et al. Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters. J Clin Invest 1997;99:2100-2109.
202. Newgaard C, Clark S, BeltrandelRio H, Hohmeier H, Quaade C, Normington K. Engineered cell lines for insulin replacement in diabetes: current status and future prospects. Diabetologia 1997;40:42-47.
203. Lee HC, Kim SJ, Kim KS, Shin HC, Yoon JW. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. Nature 2000;408:483-488.
204. Cheung AT, et al. Glucose-dependent insulin release from genetically engineered K cells. Science 2000;290:1959-1962.
205. Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 2000;49:157-162.
206. Kojima H, et al. NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nat Med 2003;9:596-603.
207. Hess D, et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 2003;21:763-770.
208. Cowan PJ, et al. High-level co-expression of complement regulators on vascular endothelium in transgenic mice: CD55 and CD59 provide greater protection from human complement-mediated injury than CD59 alone. Xenotransplantation 1998;5:184-190.
209. Cozzi E, White DJ. The generation of transgenic pigs as potential organ donors for humans. Nat Med 1995;1:964-966.
210. McCurry KR, Kooyman DL, Diamond LE, Byrne GW, Logan JS, Platt JL. Transgenic expression of human complement regulatory proteins in mice results in diminished complement deposition during organ xenoperfusion. Transplantation 1995;59:1177-1182.
211. McKenzie I, Koulmanda M, Sandrin M, Mandel T. Expression of gal(1,3)gal by porcine islet cells and its relevance to xenotransplantation. Xenotransplantation 1996;2:139-142.
212. Menger MD, Vajkoczy P, Beger C, Messmer K. Orientation of microvascular blood flow in pancreatic islet isografts. J Clin Invest 1994;93:2280-2285.
213. Groth CG, et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet 1994;344:1402-1404.
214. Korbutt GS, Elliott JF, Ao Z, Smith DK, Warnock GL, Rajotte RV. Large scale isolation, growth, and function of porcine neonatal islet cells. J Clin Invest 1996;97:2119-2129.
215. Korbutt G, et al. Natural human antibody-mediated destruction of porcine neonatal islet cell grafts. Xenotransplantation 1996;3:207-216.
216. Blusch JH, Patience C, Takeuchi Y, Templin C, Roos C, Von Der Helm K, et al. Infection of nonhuman primate cells by pig endogenous retrovirus. J Virol 2000;74:7687-7690.
217. Patience C, Takeuchi Y, Weiss R. Infection of human cells by an endogenous retrovirus of pigs. Nat Med 1997;3:282-286.
218. van der Laan LJ, et al. Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice. Nature 2000;407:90-94.
219. Valdes R. Xenotransplantation trials. Lancet 2002;359:2281.
220. Birmingham K. Skepticism surrounds diabetes xenograft experiment. Nat Med 2002;8:1047.
221. Ricordi C, et al. Human islet allografts in patients with type 2 diabetes undergoing liver transplantation. Transplantation 1997;63:473-475.