Adhesion of human hematopoietic progenitor cells to mesenchymal stromal cells involves CD44.
BACKGROUND
Direct cell-cell contact between hematopoietic progenitor cells (HPC) and their cellular microenvironment is essential for maintenance of 'stemness'. We have previously demonstrated that a feeder layer of human mesenchymal stromal cells (MSC) could provide a surrogate model as a niche for human HPC. Maintenance of long-term culture-initiating cells was significantly lower on fibroblasts.


METHODS
Adhesion of HPC to MSC was further analyzed using our recently described adhesion assay based on gravitational force upon inversion and in combination with specific antibodies against CD44.


RESULTS
Adhesion of KG1a and CD34+ cells was significantly reduced by administration of a monoclonal CD44 antibody and for KG1a to a greater extent than for CD34+ cells. Interaction of HPC and MSC was further analyzed by laser scanning confocal microscopy. CD44 was located on the uropod of CD34+ cells at the site of contact with MSC and both cell types were interwoven by a network of fibronectin.


CONCLUSIONS
Various adhesion proteins, including CD44, are involved in the contact of human HPC and human MSC and further analysis of the relative significance and interaction of these proteins will be crucial for the understanding of the mechanism of this specific cell-cell interaction.
Wagner
Wolfgang
W
Department of Medicine V, University of Heidelberg, Heidelberg, Germany. wolfgang_wagner@med.uni-heidelberg.de
Wein
Frederik
F
Roderburg
Christoph
C
Saffrich
Rainer
R
Diehlmann
Anke
A
Eckstein
Volker
V
Ho
Anthony D
AD
D019138:Antibodies, Blocking / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D005353:Fibronectins / Q000378:metabolism; D006112:Gravitation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects; D018613:Microscopy, Confocal; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects
D019138:Antibodies, Blocking; D018952:Antigens, CD34; D005353:Fibronectins; D018960:Hyaluronan Receptors