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[Islets of langerhans and pancreas transplantation tomorrow]
1Hôpital Laënnec, Université René Descartes Paris V.
Pancreatic tissue grafting as a substitution for insulin deficiency of diabetes is by far the most physiological therapeutic approach of the disease. Both islets and pancreatic gland have been successfully implanted in experimental animal diabetes and in patients, resulting in full normalisation of glucose homeostasis and, in animals, prevention of chronic complications. The need for heavy immunosuppressive drugs is a major drawback not yet overcome and auto and cotransplantation have limited indications. The future lies in intensive research aiming at the discovery of alternative strategies to avoid immunosuppression. Immunoprotection and immunoalteration are attempts to hide or delete harmful pancreatic antigens. Perfusion of MHC soluble donor antigens, anticytokine treatment, xenogenic bone marrow chimerism, use of genetically modified islets, intrathymic islet graft to induce donor specific unresponsiveness are among the numerous trials in progress. Parallely islet banking by cryopreservation and development of a physiological beta cell line are also needed and improving but the absence of a biological marker of pancreatic tissue rejection is a cruel lack. Even only one achievement among these trials could be enough to see the explosion of the development of pancreatic tissue graft. While waiting for that success, it could be wise to accept that such a graft can already bring an amelioration with partial insulin restoration before being able to give a complete cure. We have also to keep in mind that animal models are far away from diabetic patients and much more easy to treat. It is not an unrealistic dream to claim that a xenogenic pancreatic tissue graft without any immunosuppression will be available very soon for every diabetic patient.
Pancreatic tissue grafting as a substitution for insulin deficiency of diabetes is by far the most physiological therapeutic approach of the disease. Both islets and pancreatic gland have been successfully implanted in experimental animal diabetes and in patients, resulting in full normalisation of glucose homeostasis and, in animals, prevention of chronic complications. The need for heavy immunosuppressive drugs is a major drawback not yet overcome and auto and cotransplantation have limited indications. The future lies in intensive research aiming at the discovery of alternative strategies to avoid immunosuppression. Immunoprotection and immunoalteration are attempts to hide or delete harmful pancreatic antigens. Perfusion of MHC soluble donor antigens, anticytokine treatment, xenogenic bone marrow chimerism, use of genetically modified islets, intrathymic islet graft to induce donor specific unresponsiveness are among the numerous trials in progress. Parallely islet banking by cryopreservation and development of a physiological beta cell line are also needed and improving but the absence of a biological marker of pancreatic tissue rejection is a cruel lack. Even only one achievement among these trials could be enough to see the explosion of the development of pancreatic tissue graft. While waiting for that success, it could be wise to accept that such a graft can already bring an amelioration with partial insulin restoration before being able to give a complete cure. We have also to keep in mind that animal models are far away from diabetic patients and much more easy to treat. It is not an unrealistic dream to claim that a xenogenic pancreatic tissue graft without any immunosuppression will be available very soon for every diabetic patient.