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Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells
Robert E. Schwartz, … , Wei-Shou Hu, Catherine M. Verfaillie
Robert E. Schwartz, … , Wei-Shou Hu, Catherine M. Verfaillie
Published May 15, 2002
Citation Information: J Clin Invest. 2002;109(10):1291-1302. https://doi.org/10.1172/JCI15182.
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Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells

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Abstract

We have derived from normal human, mouse, and rat postnatal bone marrow primitive, multipotent adult progenitor cells (MAPCs) that can differentiate into most mesodermal cells and neuroectodermal cells in vitro and into all embryonic lineages in vivo. Here, we show that MAPCs can also differentiate into hepatocyte-like cells in vitro. Human, mouse, and rat MAPCs, cultured on Matrigel with FGF-4 and HGF, differentiated into epithelioid cells that expressed hepatocyte nuclear factor-3β (HNF-3β), GATA4, cytokeratin 19 (CK19), transthyretin, and α-fetoprotein by day 7, and expressed CK18, HNF-4, and HNF-1α on days 14–28. Virtually all human, as well as a majority of rodent cells stained positive for albumin and CK18 on day 21; 5% (rodent) to 25% (human) cells were binucleated by day 21. These cells also acquired functional characteristics of hepatocytes: they secreted urea and albumin, had phenobarbital-inducible cytochrome p450, could take up LDL, and stored glycogen. MAPCs, which can be expanded in vitro and maintained in an undifferentiated state for more than 100 population doublings, can thus differentiate into cells with morphological, phenotypic, and functional characteristics of hepatocytes. MAPCs may therefore be an ideal cell for in vivo therapies for liver disorders or for use in bioartificial liver devices.

Authors

Robert E. Schwartz, Morayma Reyes, Lisa Koodie, Yuehua Jiang, Mark Blackstad, Troy Lund, Todd Lenvik, Sandra Johnson, Wei-Shou Hu, Catherine M. Verfaillie

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Figure 1

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Phenotypic characterization of mMAPC differentiation to hepatocyte-like ...
Phenotypic characterization of mMAPC differentiation to hepatocyte-like cells. The mMAPCs were cultured on Matrigel at 21.5 × 103 cells/cm2 with FGF-4 and HGF for 4–14 days. Immunohistochemical localization of (a–c) CK18-FITC and HNF-3β-Cy3, (d–f) albumin-FITC and GATA4-Cy3, (g–i) αFP-FITC and HNF-1α-Cy3, on day 4, 7, and 14, and (j–l) CK18-FITC and albumin-Cy3 on day 14. Scale bar, 20 μm. Representative example of seven experiments.
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