Integrin-mediated interactions between human bone marrow stromal precursor cells 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 major pathway used by virtually all cell types to interact with different extracellular matrix components. In this study, purified populations of stromal precursor cells were isolated from the STRO-1-positive fraction of normal human marrow, by fluoresence-activated cell sorting, and then assayed for their ability to initiate clonogenic growth in the presence of various integrin ligands, Bone marrow-derived stromal progenitors displayed differential growth to fibronectin, vitronectin, and laminin, over collagen types I and III, but showed a similar affinity fur collagen type IV, The integrin heterodimers 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 coexpress with the STRO-1 antigen on the cell surface of CFU-F, using dual-color analysis. Furthermore, only a proportion of stromal precursors expressed the integrin alpha (4)beta (1), while no measurable levels of the integrin alpha (3)beta (1) could be detected. Subsequent adhesion studies using functional blocking antibodies to different integrin alpha/beta heterodimers showed that stromal cell growth on collagen, laminin, and fibronectin was mediated by multiple beta (1) integrins, In contrast, cloning efficiency in the presence of vitronectin was mediated in part by alphav beta3, When human marrow stromal cells were cultured under osteoinductive conditions, their ability to form a mineralized matrix in vitro was significantly diminished in the presence of a functional blocking monoclonal antibody to the beta (1) integrin subunit, The results of this study indicate that beta (1) integrins appear to be the predominant adhesion receptor subfamily utilized by stromal precursor cells to adhere and proliferate utilizing matrix glycoproteins commonly found in the bone marrow microenvironment and bone surfaces. Furthermore, these data suggest a possible role for the beta (1) integrin subfamily during the development of stromal precursor tells into functional osteoblast-like cells. (Bone 28: 174-181; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.