Journal article

Publication year: 2010

Pages: 267-276

Journal: Hepatology

Volume number: 51

Issue number: 1

ISSN: 0270-9139

eISSN: 1527-3350

DOI Link: https://doi.org/10.1002/hep.23274

Publisher: Lippincott, Williams & Wilkins

Abstract: 
Bone marrow (BM)-derived stem cells and CD34(+) fibrocytes are associated with fibrogenesis in several organs. In an Abcb4(-/-) mouse model for sclerosing cholangitis alpha-smooth muscle actin-positive (alpha-SMA(+)) myofibroblasts are thought to play a pivotal role in hepatic fibrogenesis. The aim of this study was 2-fold: (1) to demonstrate that the origin of an important fibrogenetic cell population is the BM; and (2) to investigate whether transplantation of BM (BM-Tx) affects liver function, staging, and grading. Surrogate markers for fibrogenesis and regulation of hepatic stellate cells (HSC) as well as progenitor-cell-derived fibrocytes in liver tissue were analyzed by quantitative real-time polymerase chain reaction (PCR) and immunohistology. After lethal irradiation of recipient mice, BM-Tx was carried out by way of tail vein injection of BM cells from marker protein donors (green fluorescent protein, GFP(+)) or Abcb4(-/-) mice as control (syngeneic Tx). Parameters of liver function were assessed serologically and histologically. Activated HSC of alpha-SMA(+)/CRP2(+) phenotype were expressed in approximate to 50% of proliferating bile ducts, whereas fibrotic liver parenchyma showed no expression thereof. Epithelial mesenchymal transfer (EMT) was visualized in the areas of proliferating bile ducts. The hematopoietic origin of CD34(+) fibrocytes was demonstrated immunohistologically in livers of BM chimeric mice. These CD34(+) cells infiltrated hepatic lobules from portal fields and developed a desmin(+) phenotype expressing collagen type 1 in fibrotic parenchyma as well as in vitro after isolation by magnetic cell separation. Transplantation of GFP(+)/Abcb4(+) BM improved liver function and staging compared with sham transplantation, but no significant differences were noticed among allogeneic and syngeneic Tx. Conclusion: The present study is the first to identify that both BM-derived fibrocytes and HSC are involved in biliary fibrogenesis in Abcb4(-/-) mice. Our data suggest that changes in immunity subsequent to BM-Tx may alter hepatic fibrosis. (HEPATOLOGY 2010;51:267-276.)

Harvard Citation style: Roderfeld, M., Rath, T., Voswinckel, R., Dierkes, C., Dietrich, H., Zahner, D., et al. (2010) Bone Marrow Transplantation Demonstrates Medullar Origin of CD34⁺ Fibrocytes and Ameliorates Hepatic Fibrosis in Abcb4^-/- Mice, Hepatology, 51(1), pp. 267-276. https://doi.org/10.1002/hep.23274

APA Citation style: Roderfeld, M., Rath, T., Voswinckel, R., Dierkes, C., Dietrich, H., Zahner, D., Graf, J., & Roeb, E. (2010). Bone Marrow Transplantation Demonstrates Medullar Origin of CD34⁺ Fibrocytes and Ameliorates Hepatic Fibrosis in Abcb4^-/- Mice. Hepatology. 51(1), 267-276. https://doi.org/10.1002/hep.23274