Strategic opportunities in clinical islet transplantation.
More than 471 patients with type 1 diabetes have received islet transplants at 43 institutions worldwide in the past 5 years. High rates of insulin independence have been observed at 1 year in the leading islet transplant centers, and an international multicenter trial has demonstrated reproducible success of the approach. Loss of insulin independence by 5 years in the majority of recipients remains of concern, and immunosuppressant drug side effects necessitate stringent inclusion criteria for islet-alone candidates that have the most severe, unstable glycemic control despite optimal insulin therapy. The advent of new immunosuppressive drugs with superior side-effect profiles (e.g., LEA29Y and FTY720) may open up opportunities for more "islet-friendly" approaches. Future opportunities to expand the donor pool using living donor islet transplantation are within reach, and will be enhanced considerably with both donor and recipient adjunctive treatment using islet-specific growth-factors.
Shapiro
A M James
AM
Clinical Islet Transplant Program, University of Alberta, Edmonton, Canada. shapiro@islet.ca
Lakey
Jonathan R T
JR
Paty
Breay W
BW
Senior
Peter A
PA
Bigam
David L
DL
Ryan
Edmond A
EA
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000639:trends*; D019520:Living Donors; D011184:Postoperative Period; D016019:Survival Analysis
D007166:Immunosuppressive Agents; D007328:Insulin