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Am J Physiol Gastrointest Liver Physiol (October 1, 2009). doi:10.1152/ajpgi.00123.2009
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Research Article

Bone marrow contributes to the population of pancreatic stellate cells in mice

Takashi Watanabe,1 Atsushi Masamune,1,* Kazuhiro Kikuta,1 Morihisa Hirota,1 Kiyoshi Kume,1 Kennichi Satoh,1 and Tooru Shimosegawa1

1Tohoku University Graduate School of Medicine

Submitted 27 March 2009 ; revision received 20 September 2009 ; accepted in final form 25 September 2009

ABSTRACT

Activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic fibrosis. The origin of activated PSCs has been thought to be transformation of quiescent PSCs residing locally in the pancreas. Recent studies have suggested that bone marrow (BM)-derived cells participate in regeneration processes in various organs. This study aimed to clarify the contribution of BM-derived cells to the population of PSCs in mice. We transplanted BM cells from male enhanced green fluorescent protein transgenic mice into female C57BL/6 mice after lethal irradiation. Eight weeks after BM transplantation, chronic pancreatitis was induced by administration of six intra-abdominal injections of cerulein (50 µg/kg body weight) at 1-h intervals, three days per week, for the total of six weeks. BM-derived cells were tracked by green fluorescent protein expression and in situ hybridization for the Y chromosome. Eight weeks after BM transplantation, BM-derived cells accounted for 8.7 % of the desmin (a marker of PSCs)-positive cells in the pancreas. We could isolate BM-derived cells which contained lipid droplets and expressed desmin. They could be transformed to myofibroblast-like cells by culture in vitro, further supporting that BM contributed to the population of quiescent PSCs. After induction of pancreatic fibrosis, BM-derived cells accounted for 20.2 % of {alpha}-smooth muscle actin-positive activated PSCs. The contribution of BM-derived cells to pancreatic ductal cells (positive for cytokeratin-19) was rare and less than 1 %. In conclusion, our results suggested that BM-derived cells contributed to the population of PSCs in mice.

pancreatitis; pancreatic fibrosis; stem cell; pancreatic cancer



* Tohoku University Graduate School of Medicine amasamune{at}int3.med.tohoku.ac.jp







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