Exp Mol Med.  2015 Oct;47(10):e187. 10.1038/emm.2015.64.

Murine Sca1+Lin- bone marrow contains an endodermal precursor population that differentiates into hepatocytes

Affiliations
  • 1Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. ksparkmd@gmail.com
  • 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. dlee5522@snu.ac.kr
  • 3Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.

Abstract

The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1+ subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.


MeSH Terms

Animals
Ataxin-1/*analysis
Bone Marrow Cells/*cytology
Cell Differentiation
Cell Proliferation
Cells, Cultured
Female
Hepatocytes/*cytology
Mice
Mice, Inbred BALB C
Ataxin-1
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