4.8 Article

Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver:: CD34+ cytokeratin 7/8+ cells express markers for stellate cells

Journal

JOURNAL OF HEPATOLOGY
Volume 40, Issue 2, Pages 261-268

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2003.11.007

Keywords

human fetal liver; cytokeratins; CD34; nerve growth factor receptor; stellate cells; hematopoietic stem cells; hepatic stem cells

Funding

  1. NIDDK NIH HHS [5 T32 DK07762-25, DK59301, K01 DK059301] Funding Source: Medline

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Background/Aims: The hematopoietic and hepatic systems are intertwined in the liver during fetal life. Cells expressing the hematopoietic stem cell marker CD34 and cytokeratin 7/8 (CK7/8) are hypothesized to be common stem cells for the hematopoietic and hepatic systems. Our aim was to determine if human fetal liver cells expressing CD34 and CK7/8 represent a common stem cell for both the hernatopoietic and hepatic systems. Methods: CD34(+)CK7/8(+) cells from midgestation livers were analyzed for the expression of various markers by flow cytometry and isolated based on their expression of CD34, nerve growth factor receptor (NGFR) and lack of CD45 expression. CD34(+)CD38(-) hematopoietic stem cells were also isolated and cultured in the presence of various hepatopoietins. Results: CD34(+)CK7/8(+) cells comprised 3.4-8.5% of the erythrocyte-depleted liver. CD34(+)CK7/8(+) cells had unique light-scatter properties compared to hematopoietic precursors and did not express most markers associated with hernatopoietic cells. They did stain with CD13, CD59, NGFR, desmin and alpha-smooth muscle actin. In culture, these cells had a stellate appearance. Cultured hernatopoietic stem cells failed to generate hepatocytes. Conclusions: CD34(+)CK7/8(+) cells are not common stem cells but rather appear to be hepatic stellate cells. A link between the hematopoietic and hepatic systems during fetal life requires further investigation. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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