title: Islet graft assessment in the Edmonton Protocol: implications for predicting long-term clinical outcome.
abstract: The success of the Edmonton Protocol for islet transplantation has provided new hope in the treatment of type 1 diabetes. This study reports on the assessment of 83 human islet grafts transplanted using the Edmonton Protocol since 1999. Cellular composition, as assessed by immunohistochemistry, showed a lower islet purity (approximately 40%) than has been reported in previous studies using dithizone staining to quantitate islet equivalents. Furthermore, grafts were found to contain substantial populations of exocrine and ductal tissue. Total cellular insulin transplanted was 8,097.6 +/- 3,164.4 microg/patient, and was significantly lower in bottom gradient layer grafts than top gradient layer or whole/combined grafts (P < 0.0005). A static incubation test for islet function gave a stimulation index of 3-4, although this measure did not correlate with posttransplant metabolic outcome. Furthermore, we confirmed a previously reported trend in which donor age affects islet yield and purity. It is important to note that a significant positive correlation was observed between the number of islet progenitor (ductal-epithelial) cells transplanted and long-term metabolic success as assessed an by intravenous glucose tolerance test at approximately 2 years posttransplant. In summary, careful assessment of islet graft composition is needed in a clinical transplantation program to accurately estimate islet purity and assess the contribution of other cell types present, such as islet progenitor cells.
authors.affiliation: Surgical Medical Research Institute, University of Alberta, Edmonton, Canada.
authors.forename: Cale N
authors.initials: CN
authors.lastname: Street
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.forename: Sharleen
authors.initials: S
authors.lastname: Imes
authors.forename: Ray V
authors.initials: RV
authors.lastname: Rajotte
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Ryan
authors.forename: James G
authors.initials: JG
authors.lastname: Lyon
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kin
authors.forename: Jose
authors.initials: J
authors.lastname: Avila
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Korbutt
mesh_terms: D000328:Adult; D000367:Age Factors; D000416:Alberta; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005500:Follow-Up Studies; D006801:Humans; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008875:Middle Aged; D013997:Time Factors; D020858:Tissue and Organ Harvesting / Q000379:methods; D016896:Treatment Outcome
chemical_list: D007328:Insulin