title: Evidence of stress in β cells obtained with laser capture microdissection from pancreases of brain dead donors.
abstract: Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolation process, and the complex events that occur during tissue culture. The current study focused upon the events that occur before the islet isolation procedure. Pancreases were obtained from brain dead donors (n = 7) with mean age 50 (11) and normal pancreatic tissue obtained at surgery done for pancreatic neoplasms (n = 7), mean age 69 (9). Frozen sections were subjected to laser capture microdissection (LCM) to obtain β-cell rich islet tissue, from which extracted RNA was analyzed with microarrays. Gene expression of the 2 groups was evaluated with differential expression analysis for genes and pathways. Marked changes were found in pathways concerned with endoplasmic reticulum stress with its unfolded protein response (UPR), apoptotic pathways and components of inflammation. In addition, there were changes in genes important for islet cell identity. These findings advance our understanding of why islets are stressed before transplantation, which may lead to strategies to reduce this stress and lead to better clinical outcomes.
authors.affiliation: a Joslin Diabetes Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Aref
authors.initials: A
authors.lastname: Ebrahimi
authors.affiliation: a Joslin Diabetes Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Jung
authors.affiliation: b Bioinformatics Core, Joslin Diabetes Center, Research Division , Boston , MA , USA.|c Department of Biomedical Engineering , Boston University , Boston , MA , USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Dreyfuss
authors.affiliation: b Bioinformatics Core, Joslin Diabetes Center, Research Division , Boston , MA , USA.|c Department of Biomedical Engineering , Boston University , Boston , MA , USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: d Massachusetts General Hospital, Department of Molecular Pathology , Harvard Medical School , Boston , MA , USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Sgroi
authors.affiliation: a Joslin Diabetes Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Bonner-Weir
authors.affiliation: a Joslin Diabetes Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D001926:Brain Death; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics*; D056811:Unfolded Protein Response / Q000235:genetics*
keywords: Beta cell stress; islet transplantation; islets; laser capture microdissection; pancreatic beta cells