Direct contact with mesenchymal stromal cells affects migratory behavior and gene expression profile of CD133+ hematopoietic stem cells during ex vivo expansion

Exp Hematol. 2009 Apr;37(4):504-13. doi: 10.1016/j.exphem.2008.12.005. Epub 2009 Feb 12.

Abstract

Objective: To investigate the impact of direct contact between mesenchymal stromal cells (MSCs) and CD133(+) hematopoietic stem cells in terms of expansion potential, differentiation, migratory capacity, and gene expression profile.

Materials and methods: CD133(+)-purified hematopoietic progenitor cells were cultured for 7 days on subconfluent MSCs supplemented with growth-factor-containing medium. After ex vivo expansion, nonadherent and adherent cells were collected and analyzed separately.

Results: The adherent cell population was less differentiated than the nonadherent fraction. CXCR4 was upregulated in the adherent fraction, which was associated with a higher migration capacity toward a stromal cell-derived factor-1 gradient. Colony-forming unit granulocyte-macrophage and long-term culture-initiation cell assays demonstrated a higher clonogenicity and repopulating capacity of the adherent fraction. Genes involved in adhesion, cell-cycle control, motility, and self-renewal were more highly expressed in the adherent fraction.

Conclusion: Adhesion and direct cell-to-cell contact with an MSC feeder layer supports ex vivo expansion, migratory potential, and stemness of CD133(+) hematopoietic progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD / metabolism*
  • Blotting, Western
  • Cell Adhesion
  • Cell Division / physiology
  • Cell Movement / physiology*
  • Flow Cytometry
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Glycoproteins / metabolism*
  • Hematopoietic Stem Cells* / cytology
  • Hematopoietic Stem Cells* / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Peptides / metabolism*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*
  • Surface Properties

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • PROM1 protein, human
  • Peptides