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Role of bone marrow derived cells in experimental chronic pancreatitis
  1. Frederic Marrache (frederic.marrache{at}
  1. Columbia University Medical Center, United States
    1. Swaroop Pendyala (spendyala{at}
    1. Rockefeller University, United States
      1. Govind Bhagat (gb96{at}
      1. Columbia University Medical Center, United States
        1. Kelly S Betz (kb2195{at}
        1. Columbia University Medical Center, United States
          1. Zhigang Song (zhs9002{at}
          1. Columbia University Medical Center, United States
            1. Timothy Cragin Wang (tcw21{at}
            1. Columbia University Medical Center, United States


              Background: Chronic pancreatitis is a known risk factor for pancreatic adenocarcinoma. Recent work from our group has pointed to a role for bone marrow-derived progenitor cells (BMDCs) in chronic inflammation based carcinogenesis. Consequently, we sought to investigate the role of BMDCs in chronic pancreatitis.

              Methods: We followed the fate of BMDCs using green fluorescent protein and 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 (+) and contributed to 5.12% +/- 1.12 of the pancreatic stellate cell population. Pancreatic stellate cells derived from the bone marrow could be activated as demonstrated by α-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).

              Conclusion: BMDCs contribute to the pancreatic stellate cells 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.

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