Matrix molecule interactions with hematopoietic stem cells.

We have reviewed some aspects of the production, distribution, and organization of fibronectin in the bone marrow ECM and discussed HSC-fibronectin interactions. Many questions remain. Which isoforms of fibronectin are produced in the bone marrow during ontogeny, normal hematopoiesis, and pathophysiologic challenges to the marrow microenvironment? Do HSCs interact with ED-A- and ED-B-containing fibronectin isoforms the same way they interact with plasma fibronectin? Are different fibronectin isoforms selectively expressed in different regions of the bone marrow, in keeping with the spatial organization of HSC and hematopoietic progenitor cell compartments? Addressing these questions may give us a better understanding of the role of fibronectin in HSC localization, proliferation, and differentiation. Considerable information regarding the synthesis and secretion of other ECM molecules by adherent stromal cells has been derived from in vitro analysis of LTBMCs [3]. As with fibronectin, much remains to be learned of the precise distribution and composition of bone marrow ECM molecules during in vivo development; how in vivo bone marrow ECM secretion, turnover, and remodeling are regulated during normal and pathologic hematopoietic states; and the nature and importance of in vivo cellular interactions that occur between PHSC and individual constituents of the bone marrow ECM.