Elsevier

Differentiation

Volume 73, Issues 9–10, December 2005, Pages 474-483
Differentiation

ORIGINAL ARTICLE
Human fibroblast-derived cell lines have characteristics of embryonic stem cells and cells of neuro-ectodermal origin

https://doi.org/10.1111/j.1432-0436.2005.00050.xGet rights and content

Abstract

Fibroblasts are the most ubiquitous cells in complex organisms. They are the main cells of stromal tissue and play an important role in repair and healing of damaged organs. Here we report new data—initially serendipitous findings—that fibroblast-derived cell line (human fetal lung derived cells, MRC-5) have the morphology, growth rate and gene expression pattern characteristic of embryonic stem cells and cells of neuro-ectodermal origin. We have developed a serum-free culture system to maintain these cells in proliferative state. We discovered that, at proliferative state, these cells express transcription factors of pluripotent cells, OCT-3/4 and REX-1, and embryonic cell surface antigens SSEA-1, SSEA-3, and SSEA-4, as well as TRA-1-60 and TRA-1-81. In addition to embryonic cell markers, the fibroblasts expressed neuroectodermal genes: Musashi-1, nestin, medium neurofilament, and β-III tubulin. RT-PCR data revealed that mesencephalic transcription factors, Nurr-1 and PTX-3, were also expressed in MRC-5 cells, and that these cells could be induced to express tyrosine hydroxylase (TH). Expression of TH followed down-regulation of genes associated with cell proliferation, OCT-3/4, REX-1, and β-catenin. These data indicate that the cells commonly known as fibroblasts have some of the characteristics of stem cells, and can be induced to become neuroectodermal cells and perhaps even mature neurons.

References (45)

  • P. Vourc'h et al.

    Isolation and characterization of cells with neurogenic potential from adult skeletal muscle

    Biochem Biophys Res Commun

    (2004)
  • D. Zechner et al.

    β-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system

    Dev Biol

    (2003)
  • D.C. Allison et al.

    Evidence for a relatively random array of human chromosomes on the mitotic ring

    J Cell Biol

    (1999)
  • N. Baal et al.

    Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood

    Thromb Haemost

    (2004)
  • M. Bocchetta et al.

    Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity

    Proc Natl Acad Sci USA

    (2000)
  • M.K. Carpenter et al.

    Properties of four human embryonic stem cell lines maintained in a feeder-free culture system

    Dev Dyn

    (2004)
  • H.Y. Chang et al.

    Diversity, topographic differentiation, and positional memory in human fibroblasts

    Proc Natl Acad Sci USA

    (2002)
  • K.M. Darcy et al.

    Mammary fibroblasts stimulate growth, alveolar morphogenesis, and functional differentiation of normal rat mammary epithelial cells

    In Vitro Cell Dev Biol Anim

    (2000)
  • C. Fathke et al.

    Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair

    Stem Cells

    (2004)
  • M.M. French et al.

    Chondrogenic differentiation of adult dermal fibroblasts

    Ann Biomed Eng

    (2004)
  • P.J. Gokhale et al.

    Brachyury is expressed by human teratocarcinoma cells in the absence of mesodermal differentiation

    Cell Growth Diff

    (2000)
  • Y. Goto et al.

    In vitro reconstitution of the tracheal epithelium

    Am J Respir Cell Mol Biol

    (1999)
  • Cited by (0)

    View full text