Islet isolation for allotransplantation: variables associated with successful islet yield and graft function

Abstract Aims/hypothesis: Efficient islet isolation is an
important prerequisite for successful clinical islet transplantation.
Although progressively improved, islet yield
and quality are, however, unpredictable and variable and
require standardisation. Methods: Since 1989 we have processed
437 pancreases using the automated method. The
donor characteristics, pancreas procurement, and digestion
and purification procedures including a wide enzyme characterisation
of these pancreases were analysed and correlated
with islet yield and transplant outcome. Results: By
univariate analysis, islet yield was significantly associated
with donor age (r=0.16; p=0.0009), BMI (r=0.19; p=0.0004), good pancreas condition (p=0.0031) and weight
(r=0.15; p=0.0056), total collagenase activity (r=0.22; p=
0.0001), adjusted collagenase activity/mg (r=0.18; p=0.0002),
collagenase activity/solution volume (r=0.18; p=0.0002)
and neutral protease activity/solution volume (r=0.14; p=
0.0029). A statistically significant contribution to the variability
of islet yield in a multivariate analysis performed on
donor variables was found for donor BMI (p=0.0008). In a
multivariate analysis performed on pancreas variables a
contribution was found for pancreas weight (p=0.0064),
and for a multivariate analysis performed on digestion variables
we found a contribution for digestion time (p=0.0048)
and total collagenase activity (p=0.0001). Twenty-four patients
with type 1 diabetes received single islet preparations
from single donors. In these patients, multivariate analyses
showed that the reduction in insulin requirement was significantly
associated with morphological aspects of islets (p=
0.0010) and that 1-month C-peptide values were associated
with islet purity (p=0.0071). Conclusions/interpretation:
These data provide baseline donor, digestion and purification
selection criteria for islet isolation using the automated
method and indicate that the morphological aspect may be a
clinically relevant measure of islets on which the decision
for transplant can be based.