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Purified hematopoietic stem cells can differentiate into hepatocytes in vivo

Abstract

The characterization of hepatic progenitor cells is of great scientific and clinical interest. Here we report that intravenous injection of adult bone marrow cells in the FAH−/− mouse, an animal model of tyrosinemia type I, rescued the mouse and restored the biochemical function of its liver. Moreover, within bone marrow, only rigorously purified hematopoietic stem cells gave rise to donor-derived hematopoietic and hepatic regeneration. This result seems to contradict the conventional assumptions of the germ layer origins of tissues such as the liver, and raises the question of whether the cells of the hematopoietic stem cell phenotype are pluripotent hematopoietic cells that retain the ability to transdifferentiate, or whether they are more primitive multipotent cells.

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Figure 1: Liver histology of the FAH−/− mice 7 months after bone marrow transplantation.
Figure 2: Isolation and CD45 expression of mouse HSCs.
Figure 3: Liver histology of FAH−/− mice 6 months after KTLS HSC transplantation.
Figure 4: Immunofluorescent staining of regenerating hepatic nodules in the FAH−/− mice.

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Acknowledgements

We thank L. Jerabek for help with the mice, A. Tsukamoto for review of the manuscript, M. Masek for optimizing staining protocols and M. Ferraz for animal care. This work was supported in part by the National Institutes of Health (I.L.W and M.G.) and the American Liver Foundation (X.W).

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Correspondence to Eric Lagasse.

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Lagasse, E., Connors, H., Al-Dhalimy, M. et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6, 1229–1234 (2000). https://doi.org/10.1038/81326

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