title: Impact of donor age and weaning status on pancreatic exocrine and endocrine tissue maturation in pigs.
abstract: BACKGROUND
  During the process of islet isolation, pancreatic enzymes are activated and released, adversely affecting islet survival and function. We hypothesize that the exocrine component of pancreases harvested from pre-weaned juvenile pigs is immature and hence pancreatic tissue from these donors is protected from injury during isolation and prolonged tissue culture.
  
  
  METHODS
  Biopsy specimens taken from pancreases harvested from neonatal (5-10 days), pre-weaned juvenile (18-22 days), weaned juvenile (45-60 days), and young adult pigs (>90 days) were fixed and stained with hematoxylin and eosin. Sections were examined under a fluorescent microscope to evaluate exocrine zymogen fluorescence intensity (ZFI) and under an electron microscope to evaluate exocrine zymogen granule density (ZGD).
  
  
  RESULTS
  Exocrine content estimation showed significantly lower ZFI and ZGD in juvenile pig pancreases (1.5 ± 0.04 U/μm(2) , ZFI; 1.03 ± 0.07 × 10(3) /100 μm(2) , ZGD) compared to young adult pigs (2.4 ± 0.05U/μm(2) , ZFI; 1.53 ± 0.08 × 10(3) /100 μm(2) ZGD). Islets in juvenile pig pancreases were on average smaller (105.2 ± 11.2 μm) than islets in young adult pigs (192 ± 7.7 μm), but their insulin content was comparable (80.9 ± 2.2% juvenile; 84.2 ± 0.3% young adult, P > 0.05). All data expressed as mean ± SEM.
  
  
  CONCLUSIONS
  Porcine islet xenotransplantation continues to make strides toward utilization in clinical trials of type 1 diabetes. Porcine donor age and weaning status influence the extent of exocrine maturation of the pancreas. Juvenile porcine pancreases may represent an alternative donor source for islet xenotransplantation as their exocrine component is relatively immature; this preserves islet viability during extended tissue culture following isolation.
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Krishnan
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Nhat
authors.initials: N
authors.lastname: Truong
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Gerges
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Miranda
authors.initials: M
authors.lastname: Stiewig
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Neel
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: KhueTu
authors.initials: K
authors.lastname: Ho-Nguyen
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Kummerfeld
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Alexander
authors.affiliation: SpringPoint Project, Minneapolis, MN, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Spizzo
authors.affiliation: SpringPoint Project, Minneapolis, MN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.
authors.forename: Clarence E
authors.initials: CE
authors.lastname: Foster
authors.affiliation: Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Monuki
authors.affiliation: Department of Surgery, University of California Irvine, Orange, CA, USA.|Department of Biomedical Engineering, University of California Irvine, Irvine, CA, USA.
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
mesh_terms: D000367:Age Factors; D000818:Animals; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D010179:Pancreas / Q000033:anatomy & histology / Q000254:growth & development* / Q000601:surgery; D022142:Secretory Vesicles; D013552:Swine; D020858:Tissue and Organ Harvesting / Q000379:methods*; D014183:Transplantation, Heterologous; D014886:Weaning
keywords: exocrine; histology; pancreas; xenotransplantation; zymogen