The tissue inhibitor of metalloproteinases-1 improves migration and adhesion of hematopoietic stem and progenitor cells
2013
Authors: Wilk CM, Schildberg FA, Lauterbach MA, Cadeddu RP, Fröbel J, Westphal V, Tolba RH, Hell SW, Czibere A, Bruns I, Haas R
CellNetworks People: Hell Stefan
Journal: Exp Hematol. 2013 Sep;41(9):823-831.e2. doi: 10.1016/j.exphem.2013.04.010

Homing and engraftment of hematopoietic stem and progenitor cells (HSPCs) during bone marrow transplantation are critically dependent on integrins such as β1-integrin. In the present study, we show that β1-integrin and the tetraspanin CD63 form a cell surface receptor complex for the soluble serum protein tissue inhibitor of metalloproteinases-1 (TIMP-1) on human CD34⁺ HSPCs. Through binding to this receptor complex, TIMP-1 activates β1-integrin, increases adhesion and migration of human CD34⁺ cells, and protects these cells from induced apoptosis. TIMP-1 stimulation in murine bone marrow mononuclear cells also promotes migration and adhesion; this is associated with augmented homing of murine mononuclear cells and of murine LSK⁺ cells during bone marrow transplantation. These results not only indicate that TIMP-1 is conducive to HSPC homing; they also identify CD63 and β1-integrin as a TIMP-1 receptor complex on HSPCs.