Published online 16 July 2009
Haematologica, Vol 94, Issue 11, 1493-1501 doi:10.3324/haematol.2009.006072
Copyright © 2009 by Ferrata Storti Foundation
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Hematopoietic Stem Cells

The integrin {alpha}9β1 on hematopoietic stem and progenitor cells: involvement in cell adhesion, proliferation and differentiation

Thomas D. Schreiber1,4, Carolin Steinl1, Mike Essl1, Harald Abele2, Konstanze Geiger1, Claudia A. Müller1, Wilhelm K. Aicher3, Gerd Klein1

1 University Medical Clinic, Center for Medical Research, Section for Transplantation Immunology and Immunohematology, University of Tübingen
2 Department of Gynecology and Obstetrics, University of Tübingen
3 Center for Regenerative Medicine, University of Tübingen, Germany

Correspondence: Gerd Klein, University Medical Clinic, Center for Medical Research, Section for Transplantation Immunology and Immunohematology, Waldhörnlestrasse 22, 72072, Tübingen, Germany. E-mail:gerd.klein{at}uni-tuebin-gen.de

Background: Hematopoietic stem and progenitor cells can interact with their microenvironment via integrins which are adhesion receptors consisting of {alpha} and β subunits. Current knowledge suggests that the integrin subunits {alpha}4 and {alpha}6 expressed on hematopoietic stem and progenitor cells have distinct roles in retaining stem cells in the bone marrow. The aim of our study was to gain insight into the expression and functions of the integrin subunits {alpha}7-{alpha}11 within the endosteal stem cell niche.

Design and Methods: Human osteoblasts isolated from trabecular bone and hematopoietic stem and progenitor cells purified from umbilical cord blood or bone marrow aspirates were analyzed for the expression of integrin {alpha}7-{alpha}11 chains by reverse transcriptase polymerase chain reaction. The involvement of the integrin {alpha}9β1 in hematopoietic stem and progenitor cell adhesion, proliferation and differentiation was analyzed in functional assays.

Results: Transcripts for all investigated integrin chains were found in primary osteoblasts. Highly purified hematopoietic stem and progenitor cells, however, expressed only transcripts encoding integrin subunits {alpha}7 and {alpha}9. Flow cytometric analysis verified extracellular expression of the integrin {alpha}9β1 on hematopoietic stem and progenitor cells. Cell-cell adhesion assays with osteoblasts and dye-labeled CD34+ hematopoietic stem and progenitor cells in the presence of function-blocking antibodies revealed a role of integrin {alpha}9 in hematopoietic stem and progenitor cell adhesion to osteoblasts. Furthermore, the addition of anti-integrin {alpha}9 antibodies significantly inhibited proliferation and in vitro differentiation of CD34+ hematopoietic stem and progenitor cells.

Conclusions: The integrin {alpha}9β1 has been identified as a new member of the integrin β1-subfamily expressed on human hematopoietic stem and progenitor cells. The functional studies strongly suggest that integrin {alpha}9β1 contributes to adhesion and differentiation of hematopoietic stem and progenitor cells in the endosteal stem cell niche.

Key words: cell adhesion, bone marrow microenvironment, hematopoietic stem and progenitor cells, osteoblasts.


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