Accessible Unlicensed Requires Authentication Published by De Gruyter June 6, 2008

Cytokine combinations differentially influence the SDF-1α-dependent migratory activity of cultivated murine hematopoietic stem and progenitor cells

Susannah H. Kassmer, Bernd Niggemann, Michael Punzel, Christine Mieck, Kurt S. Zänker and Thomas Dittmar
From the journal

Abstract

Stromal cell-derived factor-1α (SDF-1α) is a strong migratory stimulant for hematopoietic stem and progenitor cells (HSPCs). The hematopoietic cytokines thrombopoietin (TPO), Flt3-ligand (FL), stem cell factor (SCF) and interleukin 11 (IL-11) are able to stimulate amplification of primitive murine hematopoietic stem cells (HSCs) in vitro. The effects of these cytokines on SDF-1α-induced migratory activity of murine Lin-c-kit+ HSPC were analyzed by cultivation of these cells in the presence of 12 combinations of FL, TPO, SCF and IL-11. Migratory activity was measured in a three-dimensional collagen matrix using time-lapse video microscopy. Each cytokine combination had a distinct effect on SDF-1α-stimulated migratory activity. For instance, FL- and SCF-cultivated cells showed a high migratory SDF-1α response, while cells cultivated with SCF, TPO and IL-11 did not react to SDF-1α stimulation with an elevated migration rate. Our data indicate that the differences in the migratory SDF-1α response are not related to different CXCR4 expression levels, but rather to the differential engagement of the CXCR4-dependent MAPKp42/44 and PI3K signal transduction pathways. This indicates that hematopoietic cytokines can have a significant impact on SDF-1α-stimulated migratory activity and the underlying intracellular signaling processes in cultivated HSPCs.


Corresponding author

Received: 2007-10-22
Accepted: 2008-2-16
Published Online: 2008-06-06
Published in Print: 2008-07-01

©2008 by Walter de Gruyter Berlin New York