Integrin-mediated interactions between human bone marrow stromal precursorcells and the extracellular matrix

To date, the precise interactions between bone marrow stromal cells and the extracellular matrix that govern stromal cell development remain unclear. The integrin super-family of cell-surface adhesion molecules represents a m ajor pathway used by virtually all cell types to interact with different ex tracellular matrix components. In this study, purified populations of strom al precursor cells were isolated from the STRO-1-positive fraction of norma l human marrow, by fluoresence-activated cell sorting, and then assayed for their ability to initiate clonogenic growth in the presence of various int egrin ligands, Bone marrow-derived stromal progenitors displayed differenti al growth to fibronectin, vitronectin, and laminin, over collagen types I a nd III, but showed a similar affinity fur collagen type IV, The integrin he terodimers alpha (1)beta (1), alpha (2)beta (1), alpha (5)beta (1), alpha ( 6)beta (1), alpha (v)beta (3), and alpha (v)beta (5) were found to coexpres s with the STRO-1 antigen on the cell surface of CFU-F, using dual-color an alysis. Furthermore, only a proportion of stromal precursors expressed the integrin alpha (4)beta (1), while no measurable levels of the integrin alph a (3)beta (1) could be detected. Subsequent adhesion studies using function al blocking antibodies to different integrin alpha/beta heterodimers showed that stromal cell growth on collagen, laminin, and fibronectin was mediate d by multiple beta (1) integrins, In contrast, cloning efficiency in the pr esence of vitronectin was mediated in part by alphav beta3, When human marr ow stromal cells were cultured under osteoinductive conditions, their abili ty to form a mineralized matrix in vitro was significantly diminished in th e presence of a functional blocking monoclonal antibody to the beta (1) int egrin subunit, The results of this study indicate that beta (1) integrins a ppear to be the predominant adhesion receptor subfamily utilized by stromal precursor cells to adhere and proliferate utilizing matrix glycoproteins c ommonly found in the bone marrow microenvironment and bone surfaces. Furthe rmore, these data suggest a possible role for the beta (1) integrin subfami ly during the development of stromal precursor tells into functional osteob last-like cells. (Bone 28: 174-181; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.