Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells

Cell Mol Life Sci. 2005 Nov;62(21):2495-507. doi: 10.1007/s00018-005-5274-1.

Abstract

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34,+ cells and HSPCs expanded with primary hMSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Western
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Cell Proliferation*
  • Coculture Techniques
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mesoderm / cytology
  • Mesoderm / metabolism*
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thrombopoietin / genetics*
  • Thrombopoietin / physiology
  • Transduction, Genetic*
  • Transgenes

Substances

  • Membrane Proteins
  • flt3 ligand protein
  • Thrombopoietin