Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. Academic Article uri icon

Overview

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-3beta (HNF-3beta), GATA4, cytokeratin 19 (CK19), transthyretin, and alpha-fetoprotein by day 7, and expressed CK18, HNF-4, and HNF-1alpha 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

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

publication date

  • May 1, 2002

Research

keywords

  • Cell Differentiation
  • Hematopoietic Stem Cells
  • Hepatocytes

Identity

PubMed Central ID

  • PMC150983

Scopus Document Identifier

  • 0036106054

Digital Object Identifier (DOI)

  • 10.1172/JCI15182

PubMed ID

  • 12021244

Additional Document Info

volume

  • 109

issue

  • 10