Role of bone marrow-derived cells in experimental chronic pancreatitis.
BACKGROUND
Chronic pancreatitis is a known risk factor for pancreatic adenocarcinoma. Recent work has pointed to a role for bone marrow-derived progenitor cells (BMDCs) in chronic inflammation-based carcinogenesis. Consequently, the role of BMDCs in chronic pancreatitis was investigated.


METHODS
The fate of BMDCs was followed using green fluorescent protein and the Y chromosome as bone marrow markers in gender-mismatched transplanted mice treated with repeated injections of cerulein for up to 45 weeks. The phenotype of engrafted BMDCs was assessed based on the co-expression of bone marrow and pancreatic markers.


RESULTS
After 45 weeks of cerulein treatment, mice developed severe chronic pancreatitis but no preneoplastic lesions. BMDCs did engraft in the pancreas. Most of the BMDCs were desmin positive and contributed to 5.12% (1.12%) (mean (SEM)) of the pancreatic stellate cell population. Pancreatic stellate cells derived from the bone marrow could be activated, as demonstrated by alpha-smooth muscle actin expression, suggesting a role in tissue repair. BMDCs could also be found in pancreatic ducts, based on dolichos biflorus agglutinin and cytokeratin 19 stainings, but at a much lower frequency (0.62% (0.11%)).


CONCLUSIONS
BMDCs contribute to the pancreatic stellate cell population, suggesting a role in pancreatic tissue repair. In the absence of preneoplastic lesions, BMDCs contribute at a very low level to the ductal epithelium of the chronically inflamed pancreas. The role of BMDCs in pancreatic carcinogenesis remains to be defined.
Marrache
F
F
Division of Digestive and Liver Diseases, Columbia University Medical Center, 1130 St Nicholas Avenue, New York, NY 10032, USA.
Pendyala
S
S
Bhagat
G
G
Betz
K S
KS
Song
Z
Z
Wang
T C
TC
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002108:Ceruletide; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D014998:Y Chromosome
D049452:Green Fluorescent Proteins; D002108:Ceruletide