Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience.
Following the success obtained with transplantation of fresh human islets under steroid-free immunosuppression, this trial evaluated the transplantation of islets that had undergone a period of in vitro culture and the potential of tumor necrosis factor (TNF-alpha) blockade to improve islet engraftment. Subjects included 16 patients with type 1 diabetes mellitus (T1DM); half were randomly assigned to receive Infliximab immediately preceding initial infusion. Immunosuppression consisted of daclizumab induction and sirolimus/tacrolimus maintenance. Out of 16 subjects 14 achieved insulin independence with one or two islet infusions; adverse events precluded completion in two. Without supplemental infusions, 11/14 (79%) subjects were insulin independent at 1 year, 6/14 (43%) at 18 months; these same subjects remain insulin independent at 33+/-6 months. While on immunosuppression, all patients maintained graft function. Out of 14 patients, 8 suffered chronic partial graft loss, likely immunological in nature, 5 of these received supplemental infusions. Currently, 11 subjects remain on immunosuppression, 8 (73%) are insulin independent, two with supplemental infusions. Insulin independent subjects demonstrated normalization of HbA1c, fructosamine and Mean Amplitude of Glycemic Excursions (MAGE) values. No clinical benefit of infliximab was identified. These results demonstrate that transplantation of cultured human islet allografts results in reproducible insulin independence in all subjects under this immunosuppressive regimen, comparable to that of freshly transplanted islets (Edmonton protocol).
Froud
Tatiana
T
Diabetes Research Institute and Departments of Surgery and Radiology, University of Miami, Miami, FL, USA.
Ricordi
Camillo
C
Baidal
David A
DA
Hafiz
Muhammad M
MM
Ponte
Gaston
G
Cure
Pablo
P
Pileggi
Antonello
A
Poggioli
Raffaella
R
Ichii
Hirohito
H
Khan
Aisha
A
Ferreira
Jacqueline V
JV
Pugliese
Alberto
A
Esquenazi
Violet V
VV
Kenyon
Norma S
NS
Alejandro
Rodolfo
R
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D046509:Tissue Culture Techniques; D048069:Tumor Necrosis Factors / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose; D002096:C-Peptide; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007328:Insulin; D048069:Tumor Necrosis Factors; D000069285:Infliximab; D000077561:Daclizumab; D020123:Sirolimus; D016559:Tacrolimus