Future trends in islet cell transplantation.
Future trends in islet cell transplantation.
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DOI：
10.1089/15209150050194314
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发表时间：
2000-01-01
影响因子：
5.4
通讯作者：
Lakey, J R
中科院分区：
文献类型：
--
作者：
Shapiro, A M;Lakey, J R
THE RECENT DRAMATIC TRANSFORMATION in outcome of clinical islet transplantation reported by our group has secured a future for this therapy in diabetes. 1, 2 The Islet Transplant Registry had previously established a 1-year insulin independence rate of only 8% in 267 previous transplant attempts in the previous decade under cyclosporine and steroid-based immunosuppression. 3 Using a novel steroidfree combination of daclizumab, sirolimus and low-dose tacrolimus, designed to prevent autoimmune recurrence and allograft rejection while avoiding diabetogenic toxicity from highly concentrated drug delivery in the liver (the site of islet implantation), 4, 5 the 1-year rate of insulin independence rose to 100% in seven patients receiving islet-alone grafts. The “Edmonton Protocol” further optimized islet function by immediate graft processing, controlled delivery of a purified low-endotoxin collagenase enzyme and transplantation to limit cold ischemia, avoided culture and exposure to xenoproteins (fetal calf serum), and a double transplant ensured a total average of 800,000 islets (just over 11,000 islet equivalents per kg recipient body weight) into the liver via the portal vein. The protocol was designed to address a series of barriers that had limited success previously, as defined by Hering. 6 More recently the Edmonton series has been expanded to 12 patients, 100% of whom remain off insulin currently with the longest follow-up being 19.1 months. There were no episodes of acute rejection or autoimmune recurrence thus far, and based on intravenous glucose challenge these patients have approximately one fifth of normal insulin reserve, with no loss of function over time. The novel immunosuppressant regimen prevented sensitization to donor antigens, as shown by a negative panel reactive antibody (PRA) in all cases; this was of potential concern previously to patients who might one day require matching for renal transplantation. 7While there is no proof as yet that successful islet transplantation will prevent secondary diabetic complications in humans, maintenance of normal glycosylated hemoglobin and complete correction of diurnal glucose swings without graft deterioration over time provide compelling implications that islet transplantation will be at least as effective as whole pancreas transplantation in controlling and reversing early diabetic complications. 8–10 Will islet graft function be maintained in the long-term, or will patients require “top-ups” over time? The evidence is optimistic, as recent studies indicate that islet autograft and allograft function can be preserved for as long as 13 years after transplantation. 11, 12 Advances in antirejection treatments that virtually eliminate graft loss from acute or chronic rejection may eliminate the potential for islet degradation over time. 2, 13 However, longer follow-up is needed in larger numbers of patients before we can be certain that recurrent autoimmunity will not lead to graft degradation even in the face of systemic immunosuppression. 14 Long-term
