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 for collagen type IV. The integrin heterodimers α1β1, α2β1, α5β1, α6β1, αvβ3, and αvβ5 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 α4β1, while no measurable levels of the integrin α3β1 could be detected. Subsequent adhesion studies using functional blocking antibodies to different integrin α/β heterodimers showed that stromal cell growth on collagen, laminin, and fibronectin was mediated by multiple β1 integrins. In contrast, cloning efficiency in the presence of vitronectin was mediated in part by αvβ3. 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 β1 integrin subunit. The results of this study indicate that β1 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 β1 integrin subfamily during the development of stromal precursor cells into functional osteoblast-like cells.