Subject(s)
Diabetes Mellitus, Type 1/therapy , Diabetic Nephropathies/surgery , Islets of Langerhans Transplantation/methods , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Antilymphocyte Serum/therapeutic use , Azathioprine/therapeutic use , C-Peptide/blood , Cells, Cultured , Cyclosporine/therapeutic use , Humans , Immunosuppression Therapy/methods , Islets of Langerhans , Islets of Langerhans Transplantation/immunology , Islets of Langerhans Transplantation/physiology , Kidney Transplantation/immunology , Kidney Transplantation/physiology , Muromonab-CD3/therapeutic use , Postoperative Complications , Prednisone/therapeutic use , Tissue Preservation , Transplantation, Heterotopic , Transplantation, HomologousSubject(s)
C-Peptide/metabolism , Cryopreservation , Insulin/metabolism , Islets of Langerhans , Organ Preservation Solutions , Adenosine , Allopurinol , Cell Separation/methods , Culture Techniques/methods , Glutathione , Humans , Hypertonic Solutions , Insulin Secretion , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Raffinose , Time FactorsABSTRACT
Human islets were macroencapsulated in permselective hollow fiber membrane devices and successfully allotransplanted subcutaneously with > 90% viability after 2 weeks in situ. Recipients were patients with type I or type II diabetes and normal control subjects; none was immunosuppressed. Between 150 and 200 islet equivalents were implanted in each of the nine patients. No adverse patient complications were observed. Biocompatibility of devices was excellent. Insulin-positive beta-cells were confirmed in encapsulated islets recovered from the implanted devices in all patient populations including the type I diabetic patients. Glucose-stimulated insulin release could be demonstrated in vitro from recovered islets. These data demonstrate that macroencapsulated human islets can survive at the subcutaneous site and that permselective membranes can be designed to protect against both allogeneic immune responses as well as the autoimmune component of type I diabetes.
