Hepatocyte-like cells from directed differentiation of mouse bone marrow cells in vitro

Acta Pharmacol Sin. 2005 Apr;26(4):469-76. doi: 10.1111/j.1745-7254.2005.00093.x.

Abstract

Aim: To design the effective directed differentiation medium to differentiate bone marrow cells into hepatocyte-like cells.

Methods: Bone marrow cells were cultured in the directed differentiation media including fibroblast growth factor-4 (FGF-4) and oncostatin M (OSM). Hepatocyte-like cells from directed differentiation of bone marrow cells were identified through cell morphology, RNA expressions by reverse transcriptase-polymerase chain reaction (RT-PCR), protein expressions by Western blot, and hepatocellular synthesis and metabolism functions by albumin ELISA, Periodic acid-Shiff staining and urea assay.

Results: Some epithelial-like cells or polygonal cells appeared and increased in the course of the cell directed differentiation. Hepatocyte nucleur factor-3beta (HNF-3beta, albumin (ALB), cytokeratin 18 (CK18), transthyretin (TTR), glucose-6-phosphate (G-6-Pase), and tyrosine aminotransferase (TAT) mRNA were expressed in the course of the directed differentiation. The directed differentiated cells on d 21 expressed HNF-3? ALB, and CK18 proteins. The directed differentiated cells produced albumin and synthesized urea in a time-dependent manner. They could also synthesize glycogen.

Conclusion: Our differentiation media, including FGF-4 and OSM, are effective to differentiate bone marrow cells into hepatocyte-like cells, which could be used for hepatocyte resources for bioartificial liver or hepatocyte transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / biosynthesis*
  • Albumins / genetics
  • Animals
  • Bone Marrow Cells / cytology*
  • Cell Culture Techniques / methods
  • Cell Differentiation / drug effects
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / pharmacology
  • Glucose-6-Phosphate / biosynthesis
  • Glucose-6-Phosphate / genetics
  • Hepatocyte Nuclear Factor 3-beta
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Keratins / biosynthesis*
  • Keratins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Oncostatin M
  • Peptides / pharmacology
  • Prealbumin / biosynthesis
  • Prealbumin / genetics
  • Proto-Oncogene Proteins / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Albumins
  • DNA-Binding Proteins
  • Fgf4 protein, mouse
  • Fibroblast Growth Factor 4
  • Foxa2 protein, mouse
  • Nuclear Proteins
  • Osm protein, mouse
  • Peptides
  • Prealbumin
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transcription Factors
  • Oncostatin M
  • Hepatocyte Nuclear Factor 3-beta
  • Glucose-6-Phosphate
  • Fibroblast Growth Factors
  • Keratins