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New Strategies in Clinical Islet Cell Transplantation

  • Conference paper
New Concepts in Pathology and Treatment of Autoimmune Disorders

Part of the book series: Ernst Schering Research Foundation Workshop Supplement ((3368,volume 7))

  • 68 Accesses

Abstract

The availability of exogenous insulin therapy was a life-preserving advance for patients suffering from insulin-dependent diabetes mellitus (IDDM). However, it has uncovered the devastating long-term complications associated with micro- and macroangiopathy, which may lead to end-stage renal failure, lower limb amputation, or blindness [1]. Tight metabolic control, as provided by intensive insulin therapy, has been shown by the Diabetes Control and Complications Trial (DCCT) to significantly delay the occurrence of such complications [2], and to represent a fruitful long-term financial investment in terms of health care costs [3]. However, intensive therapy does not maintain constantly normal blood glucose levels, is a cumbersome modality, and is accompanied by an increased frequency of severe hypoglycemic episodes [4]. Islet replacement appears as a better way to achieve glucose control than exogenous insulin, since islets function for an entire lifetime, produce their own insulin, release it in a perfectly timed fashion and keep blood sugar levels in the normal range thanks to a built-in “glucose sensor” [5]. Currently, whole organ pancreas transplantation is an islet-replacing procedure able to provide sustained euglycemia and insulin-independence in a vast majority of recipients, with graft survival rates as high as 78% at 5 years [6].

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References

  1. Mintz DH, Alejandro R (1992) Islet cell transplantation —; A historical perspective. In: Ricordi C (ed) Pancreatic islet cell transplantation 1892–1992. One century of transplantation for diabetes. R.G. Landes, Austin, pp 1–6

    Google Scholar 

  2. The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986

    Article  Google Scholar 

  3. Herman WH, Eastman RC (1998) The effects of treatment on the direct costs of diabetes. Diabetes Care (Suppl 3) 21:C19-C24

    Google Scholar 

  4. The Diabetes Control and Complications Trial Research Group (1998) Effects of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. Ann Intern Med 128:517–523

    Article  Google Scholar 

  5. Carroll PB (1992) Anatomy and physiology of islets of Langerhans. In: Ricordi C (ed) Pancreatic islet cell transplantation 1892–1992. One century of transplantation for diabetes. R.G. Landes, Austin, pp 7–18

    Google Scholar 

  6. Sollinger HW, Odorico JS, Knechtle SJ, D’Alessandro AM, Kalayoglu M, Pirsch JD (1998) Experience with 500 simultaneous pancreas-kidney transplants. Ann Surg 228:284–296

    Article  PubMed  CAS  Google Scholar 

  7. Manske CL (1999) Risks and benefits of kidney and pancreas transplantation for diabetic patients. Diabetes Care (Suppl 2): 22:B114–B120

    Google Scholar 

  8. Hering BJ, Ricordi C (1999) Results, research priorities, and reasons for optimism: Islet transplantation for patients with type 1 diabetes. Graft 2:12–27

    Google Scholar 

  9. Oberholzer J, Triponez F, Lou J, Morel P (1999) Clinical islet transplantation: a review. Ann NY Acad Sci 875:189–199

    Article  PubMed  CAS  Google Scholar 

  10. Kenyon NS, Ranuncoli A, Masetti M, Chatzipetrou M, Ricordi C (1998) Islet transplantation: present and future perspectives. Diabetes Metab Rev 14:303–313

    Article  PubMed  CAS  Google Scholar 

  11. Groth CG, Korsgren O, Tibell A, Tollemar J, Möller E, Bolinder J, Östman J, Reinholt FP, Hellerström C, Andersson A (1994) Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344:1402–1404

    Article  PubMed  CAS  Google Scholar 

  12. Newgard CB, Clark S, Beltrandelrio H, Hohmeier HE, Quaade C, Normington K (1997) Engineered cell lines for insulin replacement in diabetes -current status and future prospects. Diabetologia 40 Suppl 2:S42–47

    Article  PubMed  CAS  Google Scholar 

  13. Hayek A, Beattie GM, Cirulli V, Lopez AD, Ricordi C, Rubin JS (1995) Growth factor/matrix-induced proliferation of human adult beta-cells. Diabetes 44:1458–1460

    Article  PubMed  CAS  Google Scholar 

  14. Waldmann H (1999) Transplantation tolerance: where do we stand? Nature Med 11:1245–1248

    Google Scholar 

  15. Berney T, Ricordi C (1999) Immunoisolation of cells and tissues for transplantation. Cell Transplant 8:577–579

    PubMed  CAS  Google Scholar 

  16. Soon-Shiong P, Heintz RE, Merideth N, Yao QX, Zheng T, Murphy M, Moloney MK, Schmehl M, Harris M, Mendez R, Mendez R, Sandford PA (1994) Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 343:950–951

    Article  PubMed  CAS  Google Scholar 

  17. Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW (1988) Automated method for isolation of human pancreatic islets. Diabetes 37:413–420

    Article  PubMed  CAS  Google Scholar 

  18. International Islet Transplant Registry (1999) In: Brendel MD, Hering BJ, Schultz AO, Bretzel RG (eds) Newsletter No 8. Justus-Liebig-University of Giessen, Giessen

    Google Scholar 

  19. Scharp DW, Lacy PE, Santiago JV, McCullough CS, Weide LG, Falqui L, Marchetti P, Gingerich RL, Jaffe AS, Cryer PE, Anderson CB, Flye MW (1990) Insulin independence after islet transplantation into type I diabetic patient. Diabetes 39:515–518

    Article  PubMed  CAS  Google Scholar 

  20. Tzakis A, Ricordi C, Alejandro R, Zeng Y, Fung J, Todo S, Demetris A, Mintz D, Starzl T (1990) Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet 336:402–105

    Article  PubMed  CAS  Google Scholar 

  21. Ricordi C, Tzakis AG, Carroll PB, Zeng Y, Rilo HLR, Alejandro R, Shapiro R, Fung JJ, Demetris AJ, Mintz DH, Starzl TE (1992) Human islet isolation and allotransplantation in 22 consecutive cases. Transplantation 53:407–414

    Article  PubMed  CAS  Google Scholar 

  22. Ricordi C (1996) Human islet cell transplantation: new perspectives for an old challenge. Diabetes Reviews 4:356–369

    Google Scholar 

  23. Meyer C, Hering BJ, Grossmann R, Brandhorst H, Brandhorst D, Gerich J, Federlin K, Bretzel RG (1998) Improved glucose counterregulation and autonomic symptoms after intraportal islet transplants alone in patients with long-standing type I diabetes mellitus. Transplantation 66:233–240

    Article  PubMed  CAS  Google Scholar 

  24. Alejandro R, Lehmann R, Ricordi C, Angelico MC, Kenyon NS, Burke G, Esquenazi V, Nery J, Betancourt AE, Kong SS, Miller J and Mintz DH (1997) Long-term function (6 years) of islet allografts in type 1 diabetes mellitus. Diabetes 46:1983–1989

    Article  PubMed  CAS  Google Scholar 

  25. Vargas F, Vives-Pi M, Somoza N, Armengol P, Alcalde L, Marti M, Costa M, Serradell L, Dominguez O, Fernandez-Llamazares J, Julian JF, Sanmarti A, Pujol-Borrell R (1998) Endotoxin contamination may be responsible for the unexplained failure of human pancreatic islet transplantation. Transplantation 65:722–727

    Article  PubMed  CAS  Google Scholar 

  26. Linetsky E, Inverardi L, Kenyon NS, Alejandro R, Ricordi C (1998) Endotoxin contamination of reagents used during isolation and purification of human pancreatic islets. Transplant Proc 30:345–346

    Article  PubMed  CAS  Google Scholar 

  27. Jahr H, Pfeiffer G, Hering BJ, Federlin K, Bretzel RG (1999) Endotoxin-mediated activation of cytokine production in human PBMCs by col-lagenase and Ficoll. J Mol Med 77:118–120

    Article  PubMed  CAS  Google Scholar 

  28. Linetsky E, Bottino R, Lehmann R, Alejandro R, Inverardi L, Ricordi C (1997) Improved human islet isolation using a new enzyme blend, liberase. Diabetes 46:1120–1123

    Article  PubMed  CAS  Google Scholar 

  29. Hering BJ, Bretzel RG, Hopt UT, Brandhorst H, Brandhorst D, Bollen CC, Raptis G, Helf F, Grossmann R, Meliert J, Ernst W, Scheuermann EH, Schoeppe W, Rau W, Federlin K (1994) New protocol toward prevention of early human islet allograft failure. Transplant Proc 26:570–571

    PubMed  CAS  Google Scholar 

  30. Bretzel RG, Brandhorst D, Brandhorst H, Echard M, Ernst W, Friemann S, Rau W, Weimar B, Rauber K, Hering BJ, Brendel MD (1999) Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management. J Mol Med 77:140–143

    Article  PubMed  CAS  Google Scholar 

  31. Kaufman DB, Platt JL, Rabe FL, Dunn DL, Bach FH, Sutherland DER (1990) Differential roles of Mac-1+ cells, and CD4+ and CD8+ T lymphocytes in primary nonfunction and classical rejection of islet allografts. J Exp Med 172:291–302

    Article  PubMed  CAS  Google Scholar 

  32. Bottino R, Fernandez LA, Ricordi C, Lehmann R, Tsan MF, Oliver R, Inverardi L (1998) Transplantation of allogeneic islets of Langerhans in the rat liver. Effects of macrophage depletion on graft survival and microenvi-ronment activation. Diabetes 47:316–323

    Article  PubMed  CAS  Google Scholar 

  33. Menger MD, Vajkoczy P, Leiderer R, Jager S, Messmer K (1992) Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts. J Clin Invest 90:1361–1369

    Article  PubMed  CAS  Google Scholar 

  34. Shapiro AM, Gallant H, Hao E, Wong J, Rajotte R, Yatscoff R, Kneteman N (1997) Portal vein immunosuppressant levels and islet graft toxicity. Transplant Proc 30:641

    Article  Google Scholar 

  35. Sutherland DER, Goetz FC, Sibley RK (1989) Recurrence of disease in pancreas transplants. Diabetes 38: 85–87

    PubMed  Google Scholar 

  36. Jaeger C, Brendel M, Hering BJ, Eckhard M, Bretzel RG (1997) Progressive islet graft failure occurs significantly earlier in autoantibody-positive than in autoantibody-negative IDDM recipients of intrahepatic islet allografts. Diabetes 46:1907–1910

    Article  PubMed  CAS  Google Scholar 

  37. Halloran PF, Homik J, Goes N, Lui SL, Urmson J, Ramassar V, Cockfield SM (1997) The “injury response”: a concept linking nonspecific injury, acute rejection, and long-term transplant outcomes. Transplant Proc 29:79–81

    Article  PubMed  CAS  Google Scholar 

  38. Schwartz RH (1992) Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71:1065–1068

    Article  PubMed  CAS  Google Scholar 

  39. Chen C, Nabavi N (1994) In vitro induction of T cell anergy by blocking B7 and early T cell costimulatory molecule ETC-1/B7–2. Immunity 1:147–154

    Article  PubMed  CAS  Google Scholar 

  40. Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA (1992) Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig. Science 257:789–792

    Article  PubMed  CAS  Google Scholar 

  41. Levisetti MG, Padrid PA, Szot GL, Mittal N, Meehan SM, Wardrip CL, Gray GS, Bruce DS, Thistlethwaite JR, Bluestone JA (1997) Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol 159:5187–5191

    PubMed  CAS  Google Scholar 

  42. Harlan MH, Kirk AD (1998) Anti-CD 154 therapy to prevent graft rejection. Graft 1:63–70

    Google Scholar 

  43. Kiener PA, Moran-Davis P, Rankin BM, Wahl AF, Aruffo A, Hollenbaugh D (1995) Stimulation of CD40 with purified soluble gp39 induces prein-flammatory responses in human monocytes. J Immunol 155:4917–4925

    PubMed  CAS  Google Scholar 

  44. Dechanet J, Grosset C, Taupin JL, Merville P, Banchereau J, Ripoche J, Moreau JF (1997) CD40 ligand stimulates proinflammatory cytokine production by human endothelial cells. J Immunol 159:5640–5647

    PubMed  CAS  Google Scholar 

  45. Durie FH, Rava RA, Foy TM, Aruffo A, Ledbetter JA, Noelle RJ (1993) Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science 261:1328–1330

    Article  PubMed  CAS  Google Scholar 

  46. Gerritse K, Laman JD, Noelle RJ, Aruffo A, Ledbetter JA, Boersma WJ, Claassen E (1996) CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA 93:2499–2504

    Article  PubMed  CAS  Google Scholar 

  47. Balasa B, Krahl T, Patstone G, Lee J, Tisch R, McDevitt HO, Sarvetnick N (1997) CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J Immunol 159:4620–4627

    PubMed  CAS  Google Scholar 

  48. Parker DC, Greiner DL, Phillips NE, Appel MC, Steele AW, Durie FH, Noëlle RJ, Mordes JP, Rossini AA (1995) Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proc Natl Acad Sci USA 92:9560–9564

    Article  PubMed  CAS  Google Scholar 

  49. Gordon EJ, Markees TG, Phillips NE, Noelle RJ, Shultz LD, Mordes JP, Rossini AA, Greiner DL (1998) Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD 154 monoclonal antibody. Diabetes 47:1199–1206

    Article  PubMed  CAS  Google Scholar 

  50. Kenyon NS, Chatzipetrou M, Masetti M, Ranuncoli A, Oliveira M, Wagner JL, Kirk AD, Harlan DM, Burkly LC, Ricordi C (1999) Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci U S A 96:8132–8137

    Article  PubMed  CAS  Google Scholar 

  51. Kenyon NS, Fernandez LA, Lehmann R, Masetti M, Ranuncoli A, Chatzipetrou M, Iaria G, Han D, Wagner JL, Ruiz P, Berho M, Inverardi L, Alejandro R, Mintz DH, Kirk AD, Harlan DM, Burkly LC, Ricordi C (1999) Long-term survival and function of intrahepatic islet in baboons treated with humanized anti-CD154. Diabetes 48:1473–1481

    Article  PubMed  CAS  Google Scholar 

  52. Kawai T, Andrews D, Colvin RB, Sachs DH, Cosimi AB (2000) Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand. Nat Med 6:114

    Article  CAS  Google Scholar 

  53. Kirk AD, Harlan DM (2000) Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand (reply). Nat Med 6:114

    Article  CAS  Google Scholar 

  54. Snowden JA, Brooks PM, Biggs JC (1997) Haematopoietic stem cell transplantation for autoimmune diseases. Br J Haematol 99:9–22

    Article  PubMed  CAS  Google Scholar 

  55. Ikehara S, Ohtsuki H, Good RA, Asamoto H, Nakamura T, Sekita K, Muso E, Tochino Y, Ida T, Kuzuya H, Imura H, Hamashima Y (1985) Prevention of type I diabetes in nonobese diabetic mice by allogeneic bone marrow transplantation. Proc Natl Acad Sci U S A 82:7743–7747

    Article  PubMed  CAS  Google Scholar 

  56. Yasumizu R, Sugiura K, Iwai H, Inaba M, Makino S, Ida T, Imura H, Hamashima Y, Good RA, Ikehara S (1987) Treatment of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue. Proc Natl Acad Sci U S A 84:6555–6557

    Article  PubMed  CAS  Google Scholar 

  57. Tyndall A, Fassas A, Passweg J, Ruiz de Elvira C, Attal M, Brooks P, Black C, Durez P, Finke J, Forman S, Fouillard L, Furst D, Holmes JA, Joske D, Jouet JP, Kötter I, Locatelli F, Prentice HG, Marmont AM, McSweeney P, Musso M, Peter HH, Snowden JA, Sullivan K, Tichelli A, Vavriec J, Wulffraat NM, Schmitz N, Gratwohl A (1999) Autologous haematopoietic stem cell transplants for autoimmune disease — feasibility and transplant-related mortality. Bone Marrow Transplant 24:729–734

    Article  PubMed  CAS  Google Scholar 

  58. Fontes P, Rao AS, Demetris AJ, Zeevi A, Trucco M, Carroll P, Rybka W, Rudert WA, Ricordi C, Dodson F, Shapiro R, Tzakis A, Todo S, Abu-El-magd K, Jordan M, Fung JJ, Starzl TE (1994) Bone marrow augmentation of donor-cell chimerism in kidney, liver, heart, and pancreas islet transplantation. Lancet 344:151–155

    Article  PubMed  CAS  Google Scholar 

  59. Ricordi C, Murase N, Rastellini C, Behboo R, Demetris AJ, Starzl TE (1996) Indefinite survival of rat islet allografts following infusion of donor bone marrow without cytoablation. Cell Transplantation 5:53–55

    Article  PubMed  CAS  Google Scholar 

  60. Ricordi C, Karatzas T, Nery J, Webb M, Selvaggi G, Fernandez L, Khan FA, Ruiz P, Schiff E, Olson L, Fernandez H, Bean J, Miller J and Tzakis AG (1997) High dose donor bone marrow infusions in liver transplantation: The effect of timing. Transplantation 63:7–11

    Article  PubMed  CAS  Google Scholar 

  61. Garcia-Morales R, Carreno M, Matthew J, Cirocco R, Zucker K, Ciancio G, Burke G, Roth D, Temple D, Fuller L, Esquenazi V, Eskind L, Kenyon NS, Ricordi C, Tzakis A and Miller J (1998) Continuing observations on the regulatory effects of donor-specific bone marrow cell infusions and chimerism in kidney transplant recipients. Transplantation 65:956–965

    Article  PubMed  CAS  Google Scholar 

  62. Acholonu IN, Ildstad ST (1999) The role of bone marrow transplantation in tolerance: organ-specific and cellular grafts. Curr Opin Organ Transplant 4:189–196

    Article  Google Scholar 

  63. Lenschow DJ, Walunas TL, Bluestone JA (1996) The CD28/B7 system of T-cell costimulation. Annu Rev Immunol 14:233–258

    Article  PubMed  CAS  Google Scholar 

  64. Foy TF, Aruffo A, Bajorath J, Buhlmann JE, Noelle RJ (1996) immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 14:591–617

    Google Scholar 

  65. Kirk AD, Harlan DM, Armstrong NN, Davis TA, Dong Y, Gray GS, Hong X, Thomas D, Fechner Jr JH, Knechtle SJ (1997) CTLA4-Ig and anti- CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci U S A 94:8789–8794

    Article  PubMed  CAS  Google Scholar 

  66. Kawai T, Cosimi AB, Colvin RB, Powelson J, Eason J, Kozlowski T, Sykes M, Monroy R, Tanaka M, Sachs DH (1995) Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys. Transplantation 59:256–262

    PubMed  CAS  Google Scholar 

  67. Saitovitch D, Bushell A, Mabbs DW, Morris PJ, Wood KJ (1996) Kinetics of induction of transplantation tolerance with a non-depleting anti-Cd4 monoclonal antibody and donor-specific transfusion before transplantation. Transplantation 61:1642–1647

    Article  PubMed  CAS  Google Scholar 

  68. Parker DC, Greiner DL, Phillips NE, Appel MC, Steele AW, Durie FH, Noëlle RJ, Mordes JP, Rossini AA (1995) Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proc Natl Acad Sci USA 92:9560–9564

    Article  PubMed  CAS  Google Scholar 

  69. Gordon EJ, Markees TG, Phillips NE, Noelle RJ, Shultz LD, Mordes JP, Rossini AA, Greiner DL (1998) Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD 154 monoclonal antibody. Diabetes 47:1199–1206

    Article  PubMed  CAS  Google Scholar 

  70. Rossini AA, Mordes JP, Markees TJ, Phillips NE, Gordon EJ, Greiner DL (1999) Induction of islet transplantation tolerance using donor specific transfusion and anti-CD 154 monoclonal antibody. Transplant Proc 31:629–632

    Article  PubMed  CAS  Google Scholar 

  71. Wekerle T, Sayegh MH, Hill J, Zhao Y, Chandraker A, Swenson KG, Zhao G, Sykes M (1998) Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance. J Exp Med 187:2037–2044

    Article  PubMed  CAS  Google Scholar 

  72. Wells AD, Li XC, Li Y, Walsh MC, Zheng XX, Wu Z, Nunez G, Tang A, Sayegh M, Hancock WW, Strom TB, Turka LA (1999) Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Nat Med 5:1303–1307

    Article  PubMed  CAS  Google Scholar 

  73. Ferguson TA, Green DR (1999) T cells are just dying to accept grafts. Nat Med 5:1231–1232

    Article  PubMed  CAS  Google Scholar 

  74. Li Y, Li XC, Zheng XX, Wells AD, Turka LA, Strom TB (1999) Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of allore-active T cells and induction of peripheral allograft tolerance. Nat Med 5:1298–1302

    Article  PubMed  CAS  Google Scholar 

  75. Blancho G, Cantarovich D, Soulillou JP (1999) Induction therapy with new monoclonal antibodies. Curr Opin Organ Transplantation 4:326–332

    Article  Google Scholar 

  76. Li XC, Ima A, Li Y, Zheng XX, Malek TR, Strom TB (2000) Blocking the common y-chain of cytokine receptors induces T cell apoptosis and long-term islet allograft survival. J Immunol 164:1193–1199

    PubMed  CAS  Google Scholar 

  77. Kaufman DB, Gores PF, Field MJ, Farney AC, Gruber SA, Stephanian E, Sutherland DE (1994) Effect of 15-deoxyspergualin on immediate function and long-term survival of transplanted islets in murine recipients of a marginal islet mass. Diabetes 43:778–783

    Article  PubMed  CAS  Google Scholar 

  78. Fürst DE, Keystone E, Maini RN, Smolen JS (1999) Recapitulation of the round-table discussion-assessing the role of anti-tumour necrosis factor therapy in the treatment of rheumatoid arthritis. Rheumatology 38 Suppl 2:50–53

    Google Scholar 

  79. Yasunami Y, Lacy PE, Finke EH (1983) A new site for islet transplanta-tion-a peritoneal-omental pouch. Transplantation 36:181–182

    Article  PubMed  CAS  Google Scholar 

  80. Ricordi C, Rilo H, Fontes P, Nussler A, Carroll P, Ildstad ST, Tzakis A, Starzl TE (1993) Intrapancreatic islet transplantation as a potential solution to chronic failure of intraportal islet grafts. Transplant Proc 25:988.

    PubMed  Google Scholar 

  81. Wang RN, Rosenberg L (1999) Maintenance of beta-cell function and survival following islet isolation requires re-establishment of the islet-matrix relationship. J Endocrinol 163:181–190

    Article  PubMed  CAS  Google Scholar 

  82. Richards J, Auger J, Peace D, Gale D, Michel J, Koons A, Haverty T, Zivin R, Jolliffe L, Bluestone JA (1999) Phase I evaluation of humanized OKT3: toxicity and immunomodulatory effects of hOKT3gamma4. Cancer Res 59:2096–2101

    PubMed  CAS  Google Scholar 

  83. Thomas FT, Ricordi C, Contreras JL, Hubbard WJ, Jiang XL, Eckhoff DE, Cartner S, Bilbao G, Neville DM Jr, Thomas JM (1999) Reversal of naturally occurring diabetes in primates by unmodified islet xenografts without chronic immunosuppression. Transplantation 67:846–854

    Article  PubMed  CAS  Google Scholar 

  84. Rothstein DM, Basadonna GP (1999) Anti-CD45. A new approach towards tolerance induction. Graft 2:239–245

    Google Scholar 

  85. Fridkis-Hareli M, Neveu JM, Robinson RA, Lane WS, Gauthier L, Wucherpfennig KW, Sela M, Strominger JL (1999) Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules. J Immunol 162:4697–4704

    PubMed  CAS  Google Scholar 

  86. Ossevoort MA, Ringers J, Kuhn EM, Boon L, Loire K, van den Hout Y, Bruijn JA, de Boer M, Jonker M, de Waele P (1999) Prevention of renal allograft rejection in primates by blocking the B7/CD28 pathway. Transplantation 68:1010–1018

    Article  PubMed  CAS  Google Scholar 

  87. Elder RT, Xu X, Williams JW, Gong H, Finnegan A, Chong AS (1997) The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms. J Immunol 159:22–27

    PubMed  CAS  Google Scholar 

  88. http://www.immunetolerance.orgurl Internet site.

  89. Cozzi E, Tucker AW, Langford GA, Pino-Chavez G, Wright L, O’Connell MJ, Young VJ, Lancaster R, McLaughlin M, Hunt K, Bordin MC, White DJ (1997) Characterization of pigs transgenic for human decay-accelerating factor. Transplantation 64:1383–1392

    Article  PubMed  CAS  Google Scholar 

  90. Paradis K, Langford G, Long Z, Heneine W, Sandstrom P, Switzer WM, Chapman LE, Lockey C, Onions D, Otto E (1999) Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. Science 285:1236–1241

    Article  PubMed  CAS  Google Scholar 

  91. Simone EA, Wegmann DR, Eisenbarth GS (1999) Immunologic “vaccination” for the prevention of autoimmune diabetes (type 1 A). Diabetes Care 22 Suppl 2:B7–15

    Google Scholar 

  92. Xu G, Stoffers DA, Habener JF, Bonner-Weir S (1999) Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48:2270–2276

    Article  PubMed  CAS  Google Scholar 

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  1. T. Berney
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  2. C. Ricordi
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Editors and Affiliations

  1. Clinical Neurology II, Department of Neurological Sciences, Universita la Sapienza, Viale Universita 30, 00185, Rome, Italy

    C. Pozzilli

  2. Unit for Prevention of Diabetes and Metabolic Diseases, University Campus Bio-Medico, Via Emilio Longoni, 83, 00155, Rome, Italy

    P. Pozzilli

  3. Schering AG, Müllerstrasse 178, 13342, Berlin, Germany

    J.-F. Kapp

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Berney, T., Ricordi, C. (2001). New Strategies in Clinical Islet Cell Transplantation. In: Pozzilli, C., Pozzilli, P., Kapp, JF. (eds) New Concepts in Pathology and Treatment of Autoimmune Disorders. Ernst Schering Research Foundation Workshop Supplement, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04450-6_7

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