Haematopoietic and stromal stem cell regulation by extracellular matrix components and growth factors

During human embryogenesis, differentiation of haematopoietic stem cells (HSCs) and their progeny is regulated spatially and temporally. In the adult, hemopoiesis is restricted to bone marrow (BM) which contains HSCs residing within the so-called 'niches'. These are microenvironments consisting of extracellular matrix (ECM) macromolecules (mainly glycosaminoglycans, proteoglycans, fibronectin and collagens) and stromal cells that act in concert to keep HSCs in quiescence or to promote their growth and differentiation, since BM stromal cells secrete specific growth factors acting on responsive stem cells. Haematopoietic precursors also secrete numerous regulatory molecules as fibroblast growth factors (FGF), interleukin 1 (IL1), and transforming growth factor-beta1 (TGFbeta1), regulating in an autocrine and/or paracrine manner the various stages of normal hematopoiesis. Although the majority of stem cells are quiescent and do nor respond to external signals, a few active stem cells responde to paracrine produced growth factors and differentiate into the more committed CD34+ haematopoietic stem cell or into a mesenchymal stem cell, which generate even more specified tissue. This review focuses on the role of both ECM molecules and growth factors that form a dynamic, interactive system crucial for lineage commitment and amplification. In this perspective, we recently described the pivotal role of ECM, FGF and TGFbeta on the GM-490 phenotype, which is a cell line established from the bone marrow of a patient with acute lymphoblastic leukemia. Our findings indicated the GM-490 cell line possess characteristics of both haematopoietic and mesenchymal precursors.