title: Analysis of large-scale nonhuman primate islet isolations.
abstract: OBJECTIVE
  It is important to have clinically relevant large animal models, especially nonhuman primates, to improve the efficacy of islet isolation and transplantation prior to clinical trials. The aim of this study was to improve the efficacy of islet isolation by analyzing large-scale nonhuman primate islet isolations.
  
  
  METHODS
  Sixty-one islet isolations were evaluated using nonhuman primates. An automated isolation method was scaled down for islet isolation. Islet yields of prepurification, postpurification, and postculture, purity of islets, viability of islets, and functionality with glucose stimulation test were assessed. Initially, we analyzed relationships between endpoints then analyzed additional factors for successful islet isolation. Those factors included donor characteristics, the two-layer method (TLM) of pancreas preservation, trypsin inhibition during digestion, and digestion and collection time.
  
  
  RESULTS
  Prepurification islet yields were strongly correlated with postpurification yields and postculture yields. It weakly but significantly correlated with purity, viability, and functionality. The average prepurification yield was 16,267 IE/g with each case divided into either above-average (high-yield group) or below-average groups (low-yield group). In 8 cases, TLM and trypsin inhibition were used and all cases belonged to the high-yield group. There were no significant differences between high- and low-yield groups in terms of donor age, body weight, pancreas weight, and cold ischemic time. The high-yield group had significantly longer digestion times and shorter collection times.
  
  
  CONCLUSIONS
  TLM, trypsin inhibition, complete digestion, and quick collections were key for successful islet isolation. Analysis of nonhuman primate islet isolation techniques provided useful information, which should help to improve clinical islet transplantation.
authors.affiliation: Kyoto University Hospital, Kyoto, Japan. shinichi@kuhp.kyoto-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: T
authors.initials: T
authors.lastname: Okitsu
authors.forename: H
authors.initials: H
authors.lastname: Noguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: D M
authors.initials: DM
authors.lastname: Strong
authors.forename: J A
authors.initials: JA
authors.lastname: Reems
authors.forename: L K
authors.initials: LK
authors.lastname: Gaur
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation / Q000379:methods; D007511:Ischemia; D007515:Islets of Langerhans / Q000166:cytology*; D008254:Macaca nemestrina; D023421:Models, Animal; D009929:Organ Size; D010179:Pancreas / Q000033:anatomy & histology; D012044:Regression Analysis