Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell-cell interaction.
OBJECTIVE
The significant role of direct contact between hematopoietic progenitor cells (HPC) and the cellular microenvironment for maintaining "stemness" has been demonstrated. Human mesenchymal stem cell (MSC) feeder layers represent a surrogate model for this interaction. Specific adhesion molecules are responsible for this cell-cell contact.


METHODS
To define cell-cell contact between HPC and MSC, we have studied adhesive interaction of various fractions of HPC by using a novel assay based on gravitational force upon inversion. Adherent and nonadherent cells were separated and further analyzed with regard to gene expression and long-term hematopoietic culture initiating cell (LTC-IC) frequency.


RESULTS
HPC subsets with higher self-renewing capacity demonstrated significantly higher adherence to human MSC (CD34(+) vs CD34(-), CD34(+)/CD38(-) vs CD34(+)/CD38(+), slow dividing fraction vs fast dividing fraction). LTC-IC frequency was significantly higher in the adherent fraction than in the nonadherent fraction. Furthermore, genes coding for adhesion proteins and extracellular matrix were higher expressed in the adherent subsets of CD34(+) cells (fibronectin 1, cadherin 11, vascular cell adhesion molecule-1, connexin 43, integrin beta-like 1, and TGFBI).


CONCLUSIONS
In this study we have demonstrated that primitive subsets of HPC have higher affinity to human MSC. The essential role of specific junction proteins for stabilization of cell-cell contact is indicated by their significant higher expression.
Wagner
Wolfgang
W
Department of Medicine V, University of Heidelberg, Heidelberg, Germany.
Wein
Frederik
F
Roderburg
Christoph
C
Saffrich
Rainer
R
Faber
Anne
A
Krause
Ulf
U
Schubert
Mario
M
Benes
Vladimir
V
Eckstein
Volker
V
Maul
Holger
H
Ho
Anthony D
AD
D018952:Antigens, CD34 / Q000276:immunology; D015820:Cadherins / Q000235:genetics / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018448:Models, Immunological; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D000099222:betaIG-H3 Protein
D018952:Antigens, CD34; D015820:Cadherins; D018031:Connexin 43; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D000099222:betaIG-H3 Protein; C086960:osteoblast cadherin