The integrin  9 1 on hematopoietic stem and progenitor cells: involvement in cell adhesion, proliferation and differentiation

Background Hematopoietic stem and progenitor cells can interact with their microenvironment via integrins which are adhesion receptors consisting of alpha and beta 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 9 beta 1 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 9 beta 1 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 a9 antibodies significantly inhibited proliferation and in vitro differentiation of CD34(+) hematopoietic stem and progenitor cells. Conclusions The integrin alpha 9 beta 1 has been identified as a new member of the integrin beta 1-subfamily expressed on human hematopoietic stem and progenitor cells. The functional studies strongly suggest that integrin alpha 9 beta 1 contributes to adhesion and differentiation of hematopoietic stem and progenitor cells in the endosteal stem cell niche.