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

Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist

“…However, given the role a 4 b 1 plays in HSC mobilization and the fact that a 9 and a 4 share several ligands including VCAM-1 and trOpn, a role for a 9 b 1 in HSC mobilization would not be unexpected. Previously, in vitro studies using a 9 -blocking antibodies were found to inhibit CD34 þ cell proliferation, differentiation and adhesion to primary osteoblasts 47 . In addition, we demonstrated a 9 b 1 /trOpn interactions are potently chemotactic for HSC and blocking antibodies directed to a 9 b 1 completely inhibits the migration of HSC in vitro 16 .…”

Adhesion in the stem cell niche: biological roles and regulation

“…Adult HSCs deficient for 1 integrin show a severe defect in homing to the bone marrow niche after the elimination of endogenous HSCs by radiation, indicating that 1 integrin is required for HSCs to interact with the niche (Potocnik et al, 2000). Similarly, 4, 6 and 9 integrins are also crucial for HSC-niche interaction (Grassinger et al, 2009;Qian et al, 2006;Schreiber et al, 2009). In the skin, stem cells attach to the basal membrane via integrins 6, 1 and 4 (Watt, 2002), whereas in skeletal muscle 71 integrin is localized on the side of satellite cells facing the basal membrane component of the stem cell niche (Kuang et al, 2008).…”

“…Using neutralizing antibodies, it was demonstrated that 61 integrin helps NSCs adhere to endothelial cells in the NSC vascular niche (Shen et al, 2008). HSCs also express high levels of 4, 6, 7, 9 and 1 integrins (Grassinger et al, 2009;Potocnik et al, 2000;Schreiber et al, 2009;Voura et al, 1997). Adult HSCs deficient for 1 integrin show a severe defect in homing to the bone marrow niche after the elimination of endogenous HSCs by radiation, indicating that 1 integrin is required for HSCs to interact with the niche (Potocnik et al, 2000).…”

Parsing the niche code: the molecular mechanisms governing hematopoietic stem cell adhesion and differentiation

“…In this issue of the month, Schreiber et al add integrin α9 to the growing number of integrins that are known to influence hematopoietic stem and progenitor cell (HSPC) location, proliferation and differentiation. 3 Over time, the view of integrins has expanded from the classical model of relatively static cell-matrix adhesion molecules to incorporate a much more diverse array of functions that includes cell-cell interactions, as well as inside-out and outside-in signaling. Together, these diverse functions help regulate multiple cellular processes.…”

“…1 In addition to increased thrombin and fibrin generation, increased tissue factor activity, and increased platelet activation (Figure 1), patients with hemolytic anemias manifest thrombotic complications, including venous thromboembolism, in situ pulmonary thrombosis and stroke. [1][2][3][4][5][6][7] Furthermore, the risk of thromboembolic complications appears to be higher following splenectomy.…”