title: Beta-cell replication is increased in donor organs from young patients after prolonged life support.
abstract: OBJECTIVE
  This study assesses beta-cell replication in human donor organs and examines possible influences of the preterminal clinical conditions.
  
  
  METHODS
  beta-Cell replication was quantified in a consecutive series of n = 363 human organ donors using double immunohistochemistry for Ki67 and insulin. Uni- and multivariate analysis was used to correlate replication levels to clinical donor characteristics and histopathologic findings.
  
  
  RESULTS
  beta-Cell replication was virtually absent in most donors, with < or =0.1% Ki67-positive beta-cells in 72% of donors. A subpopulation of donors, however, showed markedly elevated levels of replication of up to 7.0% Ki67-positive beta-cells. beta-Cell replication was accompanied by the increased replication of glucagon-, somatostatin-, and CA19.9-positive cells. Prolonged life support, kidney dysfunction, relatively young donor age, inflammatory infiltration, and prolonged brain death before organ retrieval were all found to be significantly associated with an increased level (> or =90th percentile) of beta-cell replication, with the first three risk factors being independent predictors. Increased beta-cell replication was most often noted in relatively young donors (< or =25 years) who received prolonged (> or =3 days) life support (68%); in contrast, it was rare in donors with a short duration of life support regardless of age (1%). Prolonged life support was accompanied by increased levels of CD68(+) and LCA/CD45(+) infiltration in the pancreatic parenchyma.
  
  
  CONCLUSIONS
  These results indicate that preterminal clinical conditions in (young) organ donors can lead to increased inflammatory infiltration of the pancreas and to increased beta-cell replication.
authors.affiliation: Diabetes Research Center and JDRF Center for Beta Cell Therapyin Diabetes, Vrije Universiteit Brussel, Brussels, Belgiumin. tveld@vub.ac.be
authors.forename: Peter
authors.initials: P
authors.lastname: In't Veld
authors.forename: Neelke
authors.initials: N
authors.lastname: De Munck
authors.forename: Kristien
authors.initials: K
authors.lastname: Van Belle
authors.forename: Nicole
authors.initials: N
authors.lastname: Buelens
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Ling
authors.forename: Ilse
authors.initials: I
authors.lastname: Weets
authors.forename: Patrick
authors.initials: P
authors.lastname: Haentjens
authors.forename: Miriam
authors.initials: M
authors.lastname: Pipeleers-Marichal
authors.forename: Frans
authors.initials: F
authors.lastname: Gorus
authors.forename: Daniel
authors.initials: D
authors.lastname: Pipeleers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008020:Life Support Care; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D014019:Tissue Donors
chemical_list: D007328:Insulin; D019394:Ki-67 Antigen