4.2 Article

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

Journal

EXPERIMENTAL HEMATOLOGY
Volume 37, Issue 4, Pages 504-513

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2008.12.005

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Funding

  1. DFG [SFB 655]

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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 sternness of CD133(+) hematopoietic progenitor cells. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

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