Isolated Pancreas Islet Xenografting

  • F. T. Thomas


At present, short-term success has been obtained with isolated pancreas islet allografts [1,2]. Clinical success has not been obtained with islet xenografts, although at least one study suggest that the human immune response to islet xenografts may be no stronger than that to allografts in some instances [3]. Recent advances in both islet isolation techniques and suppression of xenogeneic immune reactivity have provided a measure of optimism regarding the future of islet xenografting which was not previously appropriate.


Islet Transplantation Donor Tissue Islet Isolation Multiple Donor Islet Allograft 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Scharp, D.W., Lacy, P.E., Santiago, J.V., McCullough, C.S., Weide, L.G., Falqui, L., Marchetti, P., Gingerich, R.L., Jaffe, A.S., Cryer, P.E., Anderson, C.B., Flye, M.W. Insulin independence after islet transplantation into type I diabetic patient. Diabetes. 39, 515, 1990.PubMedCrossRefGoogle Scholar
  2. 2.
    Tzakis, A.G, Ricordi, C., Alejandro, R., Zeng, Y., Fung, J.J., Todo, S., Demetris, A.J., Mintz, D.H., Starzl, T.E. Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet. 336,402, 1990.PubMedCrossRefGoogle Scholar
  3. 3.
    Kondratiev, Y.Y., Sodovnikova, N.V., Petrova, G.N., Fedotov, V.P., Bljumkin, Y.N., Ignatenko, S.N., Pankov, Y.A. Islet cell transplantation in type I diabetes mellitus: evaluation of humoral immune response. Exp. Clin. Endocrinol. 93,147, 1989.PubMedCrossRefGoogle Scholar
  4. 4.
    Weber, C., Zatrigi, A., Weil, R., Mcintosh, R., Hardy, M.A., Reemtsma, K. Pancreatic islet isografts, allografts, and xenografts: comparison of morphology and function. Surgery. 79,144, 1976.PubMedGoogle Scholar
  5. 5.
    Williams, P.W. Notes on diabetes treated with grafts of sheep’s pancreas. Br. Med. J. 2, 1303, 1893.CrossRefGoogle Scholar
  6. 6.
    Weber, C., Weil, R., Mcintosh, R., Hogle, H., Warden, G., Reemtsma, K. Xenotransplantation of piscine islets into hyperglycemic rats. Surgery. 77,208, 1975.PubMedGoogle Scholar
  7. 7.
    Eloy, R., Haffen, K., Kedinger, M., Grenier, J.F. Chick embryo pancreatic transplants reverse experimental diabetes of rats. J. Clin. Invest. 64,361, 1979.PubMedCrossRefGoogle Scholar
  8. 8.
    Lacy, P.E., Davie, J.M., Finke, E.H. Prolongation of islet xenograft survival without continuous immunosuppression. Science. 209,283, 1980.PubMedCrossRefGoogle Scholar
  9. 9.
    Reckard, C.R., Stuart, F., Schulak, J.A. Immunologic comparisons of isolated pancreatic islet and whole-organ allografts. Transplant. Proc. 11,563, 1979.PubMedGoogle Scholar
  10. 10.
    Kaufman, D.B., Rabe, F.L., Platt, J.L., Dunn, D.L., Sutherland, D.E.R. Effect of host immunomodulation on the prevention of islet allograft primary non-function in a murine model. Transplant. Proc. 22,857, 1990.PubMedGoogle Scholar
  11. 11.
    Lacy, P.E., Kostianovsky, M. A method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 16,35, 1967.PubMedGoogle Scholar
  12. 12.
    Sutherland, D.E.R., Matas, A.J., Najarian, J.S. Pancreas islet cell transplantation. Surg. C/m.N. Amer. 58,365, 1978.Google Scholar
  13. 13.
    Morris, P.J., Gray, D.W., Sutton, R. Pancreatic islet transplantation. Br. Med. Bull. 49, 224, 1989.Google Scholar
  14. 14.
    Ricordi, C., Lacy, P.E., Finke, E.H., Olack, B.J., Scharp, D.W. Automated method for isolation of human pancreatic islets. Diabetes. 37,413, 1988.PubMedCrossRefGoogle Scholar
  15. 15.
    Ricordi, C., Socci, C., Davalh, A.M., Staudacher, C., Baro, P., Vertova, A., Sassi, I., Gavazzi, F., Pozza, G., DiCarlo, V. Isolation of the elusive pig islet. Surgery. 107,688, 1990.PubMedGoogle Scholar
  16. 16.
    Calafiore, R., Basta, G., Calcinaro, F., Falorni, A., Pietropaolo, M., Avellini, L., Brunetti, P. Islands of Langerhans transplant in the treatment of diabetes mellitus: current status, indications, future perspectives. Recenti. Prog. Med. 81,94, 1990.PubMedGoogle Scholar
  17. 17.
    Hering, B.J., Romann, D., Clarius, A., Brendel, M., Bretzel, R.G., Federlin, K. Bovine islets of Langerhans: potential source for transplantation? Diabetes. 38,206, 1982.Google Scholar
  18. 18.
    Hering, B.J., Romann, D., Clarius, A., Brendel, M., Bretzel, R.G., Federlin, K. Islands of Langerhans of cattle - potential donor tissue for chnical islet transplantation? Z. Exp. Chir. Transplant. Kiinstliche Organe. 22,138, 1989.Google Scholar
  19. 19.
    Bonner-Weir, S., Fike, A.A. A dual population of islets of Langerhans in bovine pancreas. Cell Tissue Res. 206,157, 1980.PubMedCrossRefGoogle Scholar
  20. 20.
    Alejandro, R., Strasser, S., Zucker, P.F., Mintz, D.H. Isolation of pancreatic islets from dogs. Semi-automated purification on albumin gradients. Transplantation. 50, 207, 1990.PubMedCrossRefGoogle Scholar
  21. 21.
    Finegood, D.L., Warnock, G.L., Kneteman, N.M., Rajotte, R.V. Insuhn sensitivity and glucose effectiveness in long-term islet autotransplanted dogs. Diabetes. 38,189, 1989.PubMedGoogle Scholar
  22. 22.
    Rajotte, R.V., Warnock, G.L., Kneteman, Erickson, C., Ellis, D.K. Optimizing cryop– reservation of isolated islets. Transplant. Proc. 21,2638, 1989.PubMedGoogle Scholar
  23. 23.
    Tzu, W.J., Tai, J. Xenotransplantation of rat pancreatic endocrine cells in spontaneous and streptozotocin-induced diabetic monkeys. Transplant. Proc. 21,2736, 1989.Google Scholar
  24. 24.
    Selawry, H.P., Whittington, K.B., Bellgrau, D. Abdominal intratesticular islet-xenograft survival in rats. Diabetes. 38,220, 1989.PubMedGoogle Scholar
  25. 25.
    Naji, A. Personal communication, December, 1990Google Scholar
  26. 26.
    Ricker, A.T., Stockberger, S.M., Halban, P. A. In: The Immunology of Diabetes Mellitus. Jaworski, M.A. (ed.) Amsterdam, Elsevier, 1986, p. 193.Google Scholar
  27. 27.
    O’Shea, G.M., Sun, A.M. Encapsulation of rat islets of Langerhans prolongs xenograft survival in diabetic mice. Diabetes. 35,943, 1986.PubMedCrossRefGoogle Scholar
  28. 28.
    Siebers, U., Zekorn, T., Bretzel, R.G., Renardy, M., Zschocke, P., Planck, H., Federlin, K. Bioartificial pancreas: islet survival and interleukin-1 action. Transplant. Proc. 22, 2035, 1990.PubMedGoogle Scholar
  29. 29.
    Wu, Z.G., Shi, Z.Q., Lu, Z.N., Yang, H., Shi, F.Y., Zheng, X.R., Sun, A.M. In vitro culture and transplantation of encapsulated human fetal islets as an artificial endocrine pancreas. Trans. Am. Soc. Artif Intern. Organs. 35,736, 1989.CrossRefGoogle Scholar
  30. 30.
    Weber, C., Zabinski, S., Koschitzky, T., Wicher, L., Rajotte, R., D’Agati, V., Peterson, L., Norton, J., Reemtsma, K. The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in NOD mice. Transplantation. 49,396, 1990.PubMedCrossRefGoogle Scholar
  31. 31.
    Lafferty, K.J., Cooley, M., Woolnough, J., Walker, K.Z. Thyroid allograft immunogenicity is reduced after organ culture. Science. 188,259, 1975.PubMedCrossRefGoogle Scholar
  32. 32.
    Sollinger, H.W., Burkenholder, P.M., Rasmus, W.R., Bach, F.H. Prolonged survival of xenografts after organ culture. Surgery. 81,74, 1977.PubMedGoogle Scholar
  33. 33.
    Lacy, P.E., Davie, J.M., Finke, H., Scharp, D.W. Prolongation of islet allograft survival. Transplantation. 27,171, 1979.PubMedCrossRefGoogle Scholar
  34. 34.
    Stock, P.G., Ascher, N.L., Chen, S., Bumgardner, G., Field, M.J., Sutherland, D.E. The alloimmune response to murine islets occurs via indirect antigen presentation to LYT2+ and L3T4+ lymphocytes. Transplant. Proc. 22,841, 1990.PubMedGoogle Scholar
  35. 35.
    Auchincloss, H. Xenotransplantation-a review. Transplant. Rev. 46,1, 1990.Google Scholar
  36. 36.
    Thomas, F., Pittman, K. Factors in effective isolation and culture of adult pig islets (API). Submitted for publication.Google Scholar
  37. 37.
    Coulombe, M., Warnock, G., Rajotte, R. Prolongation of islet xenograft survival by cry– opreservation. Diabetes. 36,1086, 1987.PubMedCrossRefGoogle Scholar
  38. 38.
    Lafferty, K., Davie, J.M., Finke, E. Prolongation of islet xenograft survival (rat-to– mouse). Diabetes. 30,285, 1981.Google Scholar
  39. 39.
    Faustman, D.L., Stienman, R.M., Gabel, A.M. Depletion of anti-la + dendritic cells. Proc. Natl. Acad. Sci. USA. 81,3864, 1984.PubMedCrossRefGoogle Scholar
  40. 40.
    Larsen, C., Austyn, J., Morris, P. The role of graft-derived dendritic leukocytes in the rejection of vascularized organ allografts. An«. Surg. 212,308, 1990.Google Scholar
  41. 41.
    Chabot, J., Weber, C., Hardy, M., Rivera, S., Bailey-Braxton, D., Strausberg, L., Wood, M, Chow, J., Pl-Sunyer, F.X., Reemtsma, K. Synergy of ALS and UV-B in prolongation ofprimate-to-mouse islet xenograft survival. Transplant. Proc. 19,1160, 1987.PubMedGoogle Scholar
  42. 42.
    Walter, P., Lesmeister, F., Leetz, H., Schnabel, K., Feifel, G., Jaeger, S. Influence of and UVB irradiation on graft survival and function of islets of Langerhans. Diabetes. 38, Suppl. 1,288, 1989.Google Scholar
  43. 43.
    Ricordi, C., Lacy, P.E., Sterbenz, K., Davie, J.M. Low temperature culture of human islets or in vivo treatment with L3T4 antibody produces a marked prolongation of human-to-mouse islet xenograft survival. Proc. Natl. Acad. Sci. USA. 84,8080, 1987.PubMedCrossRefGoogle Scholar
  44. 44.
    Has, L., Lafferty, K., Allison, A., Eugui, E.M. RS-61443 allows islet allografting and specific tolerance induction in adult mice. Transplant. Proc. 22,876, 1990.Google Scholar
  45. 45.
    Lacy, P.E. Islet transplantation. Clin. Chem. 32/lOB, B76, 1986.Google Scholar
  46. 46.
    Kruszinska, Y., Hone, D., Morley, A., Alberti, A. Preservation of islet function and morphology in high dose streptozotocin diabetic rats. Diab. Res. 3,175, 1986.Google Scholar
  47. 47.
    Trimble, E., Karakash, C., Malaisse-Lagae, R. Effects of intraportal islet transplantation on the transplanted tissue and recipient pancreas. Diabetes. 29,341, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    Richardt, M., Menden, A, Bretzel, R., Federlin, K. Islet transplantation for experimental diabetes of the rat. B cell regeneration following transplant. Horm. Metab. Res. 16,551, 1984.PubMedCrossRefGoogle Scholar
  49. 49.
    Slipjepcevic, M., Helmke, K., Federlin, K. Islet transplantation in experimental diabetes of the rat. Horm. Metab. Res. 7,20, 1975.CrossRefGoogle Scholar
  50. 50.
    Chicheportiche, D., Darquy, S., Lepeintre, J., Capron, F., Halban, P.A., Reach, G. High– performance liquid chromotography analysis of circulating insulins distinguishes between endogenous insulin production (a potential pitfall with streptozotocin diabetic rats) and islet xenograft function. Diabetologia. 33,457, 1990.PubMedCrossRefGoogle Scholar
  51. 51.
    Terasaka, R., Lacy, P.E., Bucy, R.P., Davie, J.M. Effect of cyclosporine and low temperature culture on rejection of islet xenografts (rat-to-mouse). Transplantation. 41,661, 1986.PubMedCrossRefGoogle Scholar
  52. 52.
    Stegall, M., Chabot, J, Weber, C., Reemtsma, K., Hardy, M.A. Pancreatic islet transplantation in cynomolgus monkeys. Transplantation. 48,944, 1989.PubMedCrossRefGoogle Scholar
  53. 53.
    Nakajima, Y., Nakano, H., Nakagawa, H., Segawa, M., Shiratori, T. Effect of total lymphoid irradiation on pancreas islet xenograft survival in rats. Transplantation. 34, 98, 1982.PubMedCrossRefGoogle Scholar
  54. 54.
    Lacy, P.E. Present status of islet transplantation. Clin. Inv. Med. 10,496, 1987.Google Scholar
  55. 55.
    Simeonovic, C., Ceredio, R., Wilson, J.D. Effect of GK1.5 antibody dosage on survival of pig proislet xenografts in CD4+ T cell depleted mice. Transplantation. 49,849, 1990.PubMedCrossRefGoogle Scholar
  56. 56.
    Yosunami, Y., RYU, S., Kamei, T. Characterization of immunosuppressive activity of FK506 in rat islet allografts. Transplant Proc. 22,875, 1990.Google Scholar
  57. 57.
    Pittman, K., Thomas, F.T., Patselas, T., Thomas, J.M. Long-term (12–14 week) survival of pig islet xenografts (PIX) in Lewis rats (LR) treated with splenectomy (SPL), deoxyspergualin (DSG) and rabbit antithymocyte globulin (RATG). Submitted for publication.Google Scholar
  58. 58.
    Thomas, F. Comparative immunosuppression for xenografting. In: Xenograft25. Hardy, M.A. (ed.) Elsevier; Amsterdam, New York, Oxford, 1989, p. 55.Google Scholar
  59. 59.
    Naji, A., Barker, C. Differential susceptibility of endocrine tissues to humoral immunity. Surg. Forum. 29,349, 1978.PubMedGoogle Scholar
  60. 60.
    Delmonico, F., Chase, C., Russell, P. Transplantation of rat islets of Langerhans into diabetic mice. Transplant. Proc. 9,367, 1977.PubMedGoogle Scholar
  61. 61.
    Sutton, R., Greay, D.W., Burnett, M., McShane, P., Turner, R., Morris, P. Metabolic function of intraportal and intrasplenic islet autografts in cynomolgus monkeys. Diabetes. 38,182, 1989.PubMedCrossRefGoogle Scholar
  62. 62.
    Alejandro, R., Cutfield, R.G., Steinvold, F., Polonsky, K.S., Noel, J., Olson, L., Dillberger, J., Miller, J., Mintz, D.H. Natural history of intrahepatic canine islet cell autografts. Clin. Invest. 78,1339, 1986.CrossRefGoogle Scholar
  63. 63.
    Warnock, G.L., Rajotte, V.R., Procyshyn, A.W. Normoglycemia after reflux of islet-containing pancreas fragments into the splenic vascular bed in dogs. Diabetes. 32,452, 1983.PubMedCrossRefGoogle Scholar
  64. 64.
    Kaufman, D., Morel, D., Field, M., Tzardis, P., Munn, S.R., Sutherland, D.E. Canine islet autografts. Functional outcome as influenced by islet number and purity. Transplant. Proc. 22,771, 1990.PubMedGoogle Scholar
  65. 65.
    Kanai, T., Porter, J., Monaco, A.P., Maki, T. Sequential multiple transplantations of multiple-donor pancreatic islet allografts. Diabetes. 38, Suppl. 1,286, 1989.Google Scholar
  66. 66.
    Alejandro, R., Mintz, D.H., Noel, J., Latif, Z., Koh, N., Russell, E., Miller, J. Islet cell transplantation in type I diabetes mellitus. Transplant. Froc. 19,2359, 1987.Google Scholar
  67. 67.
    Scharp, D.W., Lacy, P., Ricordi, C., Boyle, P., Santiago, J., Cryer, P., Gingerick, R., Jaffe, A., Anderson, C., Flye, W. Human islet transplantation in patients with type I diabetes. Transplant. Proc. 21,2744, 1989.PubMedGoogle Scholar
  68. 68.
    Cicciarelli, J., Cho, R.V. Regraft kidney transplant survival. In: Clinical Transplants. Terasaki, P.I. (ed.) Los Angeles, Ucla Tissue Typing Lab, 1986, p. 285.Google Scholar
  69. 69.
    Gotoh, M., Porter, J., Kanai, T., Monaco, A.P., Maki, T. Effect of specific and nonspecific alloantigen stimulation on islet allograft survival. Transplant. Proc. 21,2746, 1989.PubMedGoogle Scholar
  70. 70.
    Kanai, T., Porter, J., Maki, T., Monaco, A.P. Possible mechanisms underlying marked graft survival following multiple donor islet allotransplantation. Transplant. Proc. In press.Google Scholar
  71. 71.
    Sachs, D., Bach, F. Immunology of xenograft rejection. Hum. Immunol. 28,245, 1990.PubMedCrossRefGoogle Scholar
  72. 72.
    Sun, A.M., O’Shea, G.M., Yuan, Z.Y., Ma., F., Cai, Z. Alio– and xenotransplantation of microencapsulated islets of Langerhans (a bioartificial pancreas). In: Advanced Models for Therapy of Insidin Dependent Diabetes. Brunetti, P., Waldhausl, W.K. (eds.) New York, Raven Press, Serono Symposia, 37,303, 1987.Google Scholar
  73. 73.
    Manns, J.G., Boda, J.M. Insulin release in lambs and aduh sheep. Am. J. Physiol. 212, 747, 1967.PubMedGoogle Scholar
  74. 74.
    Lacy, P., Ricordi, C., Finke, E. Effect of transplant site and alpha L3T4 treatment on survival of rat, hamster and rabbit islet xenografts in mice. Transplantation. 47,761, 1989.PubMedCrossRefGoogle Scholar
  75. 75.
    King, N.W., Chalifoux, L.V., Ringler, D.J., Wyand, M.S., Sehgal, P.K., Daniel, M.D., Letvin, N.L. Comparative biology of natural and experimental SIV mac infection in macaque monkeys: a review. J. Med. Primatol. 19,109, 1990.PubMedGoogle Scholar
  76. 76.
    Daniel, M.D., Letvin, N.L., Sehgal, P.K., Schmidt, D.K., Silva, D.P., Solomon, K.R., Hodi, F.S. Jr., Ringler, D.J., Hunt, R.D., King, N.W., et al. Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys. Int. J. Cancer. 41,601, 1988.PubMedCrossRefGoogle Scholar
  77. 77.
    Sibley, R.K., Sutherland, D.E.R., Goetz, F., Michael, A.F. Recurrent diabetes in the pancreas iso– and allograft. Lab. Invest. 53,132, 1985.PubMedGoogle Scholar
  78. 78.
    Mandel, T., Koulmanda, M., Loudovaris, T., Bacelj, A. Islet grafts in NOD mice — comparison of iso-alio-and pig xenografts. Transplant. Proc. 21,3813, 1989.PubMedGoogle Scholar
  79. 79.
    Kaufman, D., Platt, J., Rabe, F., Dunn, D., Bach, F., Sutherland, D.E.R. Differential roles of Moc 1+ cehs and CD4+ and CD8+ T lymphocytes in primary non-function and classic rejection of islet allografts./. Exp. Med. 172,291, 1990.CrossRefGoogle Scholar
  80. 80.
    Moses, R., Pierson, R. III, Winn, H., Auchincloss, H. Xenogeneic proliferation and lymphokine production are dependent upon CD4+ helper T cells and self-antigen presenting cells in the mouse. J. Exp. Med. 172,567, 1990.PubMedCrossRefGoogle Scholar
  81. 81.
    Ildstad, S., Wren, S., Stephany, D., Sachs, D.H. Effect of selective T cell depletions in mixed xenogeneic reconstitution on species hyporeactivity to xenogeneic transplantation. Transplantation. 41,372, 1986.PubMedCrossRefGoogle Scholar
  82. 82.
    Crowther, N., Gotfreadsen, C., Moody, A.J., Green, LC. Porcine islet isolation cellular digestion and secretory response. Horm. Met. Res. 21,590, 1989.CrossRefGoogle Scholar
  83. 83.
    Ricordi, C., Finke, E., Lacy, P.E. A method for the mass isolation of islets from the adult pig pancreas. Diabetes. 35,649, 1986.PubMedCrossRefGoogle Scholar
  84. 84.
    Ricordi, C., Socci, A., Davilh, C., Staudacher, C, Vertova, A., Baro, P., Sassi, L, Braghi, S., Giuzzi, N., Pozza, G., DiCarlo, V. Apphcation of the automated method to islet isolation in swine. Transplant. Proc. 22,784, 1990.PubMedGoogle Scholar
  85. 85.
    Hellerstrom, C., Andersson, A., Korsgren, O., Jansson, L., Sandler, S. Aspects of pancreatic islet transplantation in diabetes. Balliere’s Clin. Gastroenterol. 3,851, 1989.CrossRefGoogle Scholar
  86. 86.
    Schrezenmeir, J., Faust, P., Laue, C., Kirchgessner, J., Stallmach, T., Müntefering, H., Beyer, J. Immunoprotection in biocompatible membranes permits transplantation of piscine islets to rats. Transplant. Proc. 21,2730, 1989.PubMedGoogle Scholar
  87. 87.
    Falkmer, S. Ostberg, Y. Comparative morphology of pancreatic islets in animals. In: The Diabetic Pancreas. Volk, B.W., Arquilla, E.R. (eds.) New York, Raven Press, 1977, p. 15.Google Scholar
  88. 88.
    Alejandro, R., Cutfield, R., Schienvold, F., Polonsky, K.S., Noel, J., Olson, L., Dillberger, J., Miller, J., Mintz, D.H. Natural history of intrahepatic canine islet cell autografts./Clin. Invest. 78,1339, 1986.Google Scholar
  89. 89.
    Warnock, G., Rajotte, R. Critical mass of purified islets that induce normoglycemia after implantation in the dog. Diabetes. 37,467, 1988.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • F. T. Thomas

There are no affiliations available

Personalised recommendations