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Modeling the Iatrogenic Pancreatic Cancer Risk After Islet Autotransplantation in Mouse
Author(s) -
Dugnani E.,
Pasquale V.,
Liberati D.,
Citro A.,
Cantarelli E.,
Pellegrini S.,
Marra P.,
Canu T.,
Balzano G.,
Scavini M.,
Esposito A.,
Doglioni C.,
Piemonti L.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14360
Subject(s) - medicine , islet , autotransplantation , pancreatic cancer , gastroenterology , pancreatectomy , metastasis , pancreas , urology , pancreatitis , cancer , transplantation , pathology , diabetes mellitus , endocrinology
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk, islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL ‐Kras G12D/+ ; LSL ‐Trp53 R172H/+ ;Pdx‐1‐Cre , termed KPC mouse) were transplanted via the portal vein in syngeneic wild type ( WT ) severely diabetic recipients in the following treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal to 250 islet equivalents ( IEQ s); group B (n = 12) received 250 WT IEQ s mixed with KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQ s, and group D (n = 7) received 250 WT IEQ s. The incidence of hepatic metastasis was assessed by magnetic resonance imaging and histology over the 13 months of follow‐up. Overall survival was not different in the four groups. No mice developed liver metastases during the follow‐up. Two mice developed spontaneous tumors: a liver hepatocellular tumor in group A and a malignant lymphoma in group D. Islets and/or exocrine clusters obtained by KPC mouse, a model that develops pancreatic cancer with 100% penetrance, do not retain the same risk of tumor development when transplanted via the portal vein in a syngeneic diabetic recipient.