Τίτλος:
Development and Application of a Semi quantitative Scoring Method for
Ultrastructural Assessment of Acute Stress in Pancreatic Islet
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background. Pancreas and islet transplantation outcomes are negatively
impacted by injury to the endocrine cells from acute stress during donor
death, organ procurement, processing, and transplant procedures. Here,
we report a novel electron microscopy scoring system, the Newcastle
Pancreas Endocrine Stress Score (NPESS).
Methods. NPESS was adapted and expanded from our previously validated
method for scoring pancreatic exocrine acinar cells, yielding a 4-point
scale (0-3) classifying ultrastructural pathology in endocrine cell
nuclei, mitochondria, endoplasmic reticulum, cytoplasmic vacuolization,
and secretory granule depletion, with a maximum additive score of 15. We
applied NPESS in a cohort of deceased organ donors after brainstem (DBD)
and circulatory (DOD) death with a wide range of cold ischemic times
(3.6-35.9h) including 3 donors with type 1 and 3 with type 2 diabetes to
assess islets in situ (n = 30) in addition to pancreata (n = 3) pre- and
postislet isolation. Results. In DBD pancreata, NPESS correlated with
cold ischemic time (head: r = 0.55: P = 0.02) and mirrored exocrine
score (r = 0.48; P = 0.01). When stratified by endocrine phenotype,
cells with granules of heterogeneous morphology had higher scores than
alpha, beta, and delta cells (P < 0.0001). Cells of mixed
endocrine-exocrine morphology were observed in association with
increased NPESS (P = 0.02) . Islet isolation was associated with
improved NPESS (in situ: 8.39 +/- 0.77 [Mean +/- SD]; postisolation:
5.44 +/- 0.31; P = 0.04).
Conclusions. NPESS provides a robust method for semiquantitative scoring
of subcellular ultrastructural changes in human pancreatic endocrine
cells in situ and following islet isolation with utility for unbiased
evaluation of acute stress in organ transplantation research.
Συγγραφείς:
Dyson, Nicola J.
Kattner, Nicole
Honkanen-Scott, Minna and
Hunter, Bethany
Doyle, Jennifer A.
White, Kathryn
Davey,
Tracey S.
Ploeg, Rutger J.
Bury, Yvonne A.
Tiniakos, Dina G.
and Shaw, James A. M.
Scott, III, William E.
Περιοδικό:
TRANSPLANTATION DIRECT
Εκδότης:
Lippincott, Williams & Wilkins
DOI:
10.1097/TXD.0000000000001271
