Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis

J Hepatol. 2006 Sep;45(3):429-38. doi: 10.1016/j.jhep.2006.04.014. Epub 2006 Jun 9.


Background/aims: Hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. However, their origin is still unknown. We tested the hypothesis that bone marrow (BM) contributes to the population of HSCs.

Methods: Chimeric mice transplanted with donor BM from collagen alpha1(I)-GFP+ reporter mice were subjected to the bile duct ligation (BDL)-induced liver injury.

Results: In response to injury, BM-derived collagen-expressing GFP+ cells were detected in liver tissues of chimeric mice. However, these cells were not activated HSCs in that they did not express alpha-smooth muscle actin or desmin and could not be isolated with the HSC fraction. Meanwhile, the majority of these BM-derived cells co-expressed collagen-GFP+ and CD45+, suggesting that these cells represent a unique population of fibrocytes. Consistent with their lymphoid origin, the number of GFP+CD45+ fibrocytes found in BM and spleen of chimeric mice increased in response to injury. Fibrocytes cultured in the presence of TGF-beta1 differentiated into SMA+desmin+ collagen-producing myofibroblasts, potentially contributing to liver fibrosis.

Conclusions: In response to the BDL-induced liver injury: (i) HSCs do not originate in the BM; (ii) collagen-producing fibrocytes are recruited from the BM to damaged liver.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Desmin / genetics
  • Desmin / metabolism
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic / genetics
  • Spleen / metabolism
  • Spleen / pathology
  • Transforming Growth Factor beta / pharmacology


  • Collagen Type I
  • Desmin
  • Transforming Growth Factor beta
  • Green Fluorescent Proteins
  • Leukocyte Common Antigens