Islet graft assessment in the Edmonton Protocol: implications for predicting long-term clinical outcome.
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.
Street
Cale N
CN
Surgical Medical Research Institute, University of Alberta, Edmonton, Canada.
Lakey
Jonathan R T
JR
Shapiro
A M James
AM
Imes
Sharleen
S
Rajotte
Ray V
RV
Ryan
Edmond A
EA
Lyon
James G
JG
Kin
Tatsuya
T
Avila
Jose
J
Tsujimura
Toshiaki
T
Korbutt
Gregory S
GS
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
D007328:Insulin