Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells

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

Research output: Contribution to journalArticle

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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-1αa on days 14-28. Virtually all human, as well as a majority of rodent cells stained positive for albumin and CK18 on day 21; S% (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.

Original languageEnglish (US)
Pages (from-to)1291-1302
Number of pages12
JournalJournal of Clinical Investigation
Volume109
Issue number10
DOIs
StatePublished - 2002
Externally publishedYes

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Hepatocytes
Stem Cells
Bone Marrow
Albumins
Rodentia
Hepatocyte Nuclear Factors
Artificial Liver
Fetal Proteins
Keratin-19
Epithelioid Cells
Prealbumin
Phenobarbital
Glycogen
Cytochrome P-450 Enzyme System
Urea
Equipment and Supplies
Liver
Population
In Vitro Techniques

ASJC Scopus subject areas

  • Medicine(all)

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Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. / Schwartz, Robert E.; Reyes Gil, Morayma; Koodie, Lisa; Jiang, Yuehua; Blackstad, Mark; Lund, Troy; Lenvik, Todd; Johnson, Sandra; Hu, Wei Shou; Verfaillie, Catherine M.

In: Journal of Clinical Investigation, Vol. 109, No. 10, 2002, p. 1291-1302.

Research output: Contribution to journalArticle

Schwartz, RE, Reyes Gil, M, Koodie, L, Jiang, Y, Blackstad, M, Lund, T, Lenvik, T, Johnson, S, Hu, WS & Verfaillie, CM 2002, 'Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells', Journal of Clinical Investigation, vol. 109, no. 10, pp. 1291-1302. https://doi.org/10.1172/JCI200215182
Schwartz, Robert E. ; Reyes Gil, Morayma ; Koodie, Lisa ; Jiang, Yuehua ; Blackstad, Mark ; Lund, Troy ; Lenvik, Todd ; Johnson, Sandra ; Hu, Wei Shou ; Verfaillie, Catherine M. / Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. In: Journal of Clinical Investigation. 2002 ; Vol. 109, No. 10. pp. 1291-1302.
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