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Differentiation of bone marrow-derived cells into regenerated mesothelial cells in peritoneal remodeling using a peritoneal fibrosis mouse model
Authors:Yoshimi Sekiguchi  Chieko Hamada  Yuuki Ro  Hirotaka Nakamoto  Masanori Inaba  Tetsutaro Shimaoka  Hiroaki Io  Ichiro Koyanagi  Seiki Aruga  Jiro Inuma  Kayo Kaneko  Yoko Hotta  Peter J. Margetts  Hideki Mochizuki  Satoshi Horikoshi  Yasuhiko Tomino
Affiliation:Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo, 113-8421, Japan.
Abstract:Marked thickening of the peritoneum and vasculopathy in the submesothelial compact zone have been reported in long-term peritoneal dialysis patients. Bone marrow (BM)-derived cell lines are considered to be useful tools for therapy of various diseases. To clarify the role of BM-derived cells in the peritoneal fibrosis (PF) model, we analyzed several lineages of cells in the peritoneum. BM cells from green fluorescent protein (GFP) transgenic mice were transplanted into na?ve C57Bl/6 mice. Chlorhexidine gluconate (CG) was injected intraperitoneally to induce PF. Immunohistochemical analysis was performed with parietal peritoneum using anti-Sca-1 or -c-Kit and -GFP antibodies. Isolated BM cells were also transplanted into the CG-stimulated peritoneum. BM-derived cells from GFP transgenic mice appeared in the submesothelium from days 14 to 42. Both GFP- and stem cell marker-positive cells were observed in the submesothelium and on the surface. Isolated c-Kit-positive cells, transplanted into the peritoneal cavity, differentiated into mesothelial cells. In this study, we investigated whether or not BM-derived cells play a role in the repair of PF and immature cells have the potential of inducing repair of the peritoneum. The findings of this study suggest a new concept for therapy of PF.
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