Impact of pancreatic cold preservation on rat islet recovery and function.
BACKGROUND
Islet transplantation success depends on the number and quality of islets transplanted. This study aimed at exploring the molecular mechanisms associated with cold pancreas preservation and their impact on islet cell survival and function.


METHODS
Rat pancreata were stored in cold University of Wisconsin preservation solution for short (3 hr; control) or long (18 hr) cold ischemia times (CIT).


RESULTS
Pancreata exposed to long CIT yielded lower islet numbers and showed reduced cellular viability; isolated islets displayed higher levels of phosphorylated stress-activated protein kinase (c-jun N-terminal Kinase and Mitogen-Activated Protein Kinase-p38), and chemokine (C-C) ligand-3, and lower levels of vascular endothelial growth factor, interleukins (IL)-9 and IL-10. Islets obtained from long-CIT pancreata were functionally impaired after transplantation. Differential proteomic expression in pancreatic tissue after CIT included increased eukaryotic translation elongation factor-1-alpha-1 (apoptosis related) and reduced Clade-B (serine protease inhibitor).


CONCLUSIONS
Our study indicates that cold ischemia stimulates inflammatory pathways (chemokine (c-c)ligand-3, phosphorylation of c-jun N-terminal Kinase and mitogen-activated protein kinase-p38, and eukaryotic translation elongation factor-1-alpha-1) and decreases repair/cytoprotective pathways (IL-10, vascular endothelial growth factor, and Clade-B), all of which may negatively affect the quality and mass of islets obtained from a donor pancreas.
Pileggi
Antonello
A
Cell Transplant Center, Diabetes Research Institute, University of Miami-Leonard M. Miller School of Medicine, Miami, FL 33136, USA. APileggi@med.miami.edu
Ribeiro
Melina M
MM
Hogan
Anthony R
AR
Molano
R Damaris
RD
Cobianchi
Lorenzo
L
Ichii
Hirohito
H
Embury
Jennifer
J
Inverardi
Luca
L
Fornoni
Alessia
A
Ricordi
Camillo
C
Pastori
Ricardo L
RL
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002470:Cell Survival; D003080:Cold Temperature; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione; D006085:Graft Survival; D007328:Insulin; D007515:Islets of Langerhans / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000502:physiology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010179:Pancreas / Q000166:cytology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D020858:Tissue and Organ Harvesting / Q000379:methods
D016207:Cytokines; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D011494:Protein Kinases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose