title: Bone marrow contributes to the population of pancreatic stellate cells in mice.
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 microg/kg body wt) at 1-h intervals, 3 days per week, for the total of 6 wk. 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.
authors.affiliation: Tohoku Univ. Graduate School of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kikuta
authors.forename: Morihisa
authors.initials: M
authors.lastname: Hirota
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kume
authors.forename: Kennichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D002108:Ceruletide; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010183:Pancreatic Ducts / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000473:pathology*; D013997:Time Factors; D014998:Y Chromosome
chemical_list: D000199:Actins; D003893:Desmin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002108:Ceruletide