title: In vitro exposure of pig neonatal isletlike cell clusters to human blood.
abstract: BACKGROUND
  Pig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR).
  
  
  METHODS
  Neonatal isletlike cell clusters were harvested from three groups of piglets-(i) wild-type (genetically unmodified), (ii) α1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood in vitro, and the following measurements were made-antibody binding; complement activation; speed of islet-induced coagulation; C-peptide; glutamic acid decarboxylase (GAD65) release; viability.
  
  
  RESULTS
  Time to coagulation and viability were both reduced in all groups compared to freshly drawn non-anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups.
  
  
  CONCLUSIONS
  Neonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Nagaraju
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bertera
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, AB, Canada.
authors.forename: Gina R
authors.initials: GR
authors.lastname: Rayat
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Wijkstrom
authors.affiliation: Revivicor, Inc., Blacksburg, VA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Bottino
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001081:Apyrase / Q000235:genetics / Q000276:immunology; D001769:Blood / Q000276:immunology*; D001777:Blood Coagulation; D003167:Complement Activation; D003920:Diabetes Mellitus / Q000628:therapy; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D055786:Gene Knockout Techniques; D006801:Humans; D066298:In Vitro Techniques; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D034421:Sus scrofa; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000379:methods*
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D011994:Recombinant Proteins; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine; D001081:Apyrase; C067869:CD39 antigen
keywords: diabetes mellitus; genetically engineered; instant blood-mediated inflammatory reaction; islets; neonatal; pigs; xenotransplantation