Haematopoietic and Stromal Stem Cell Regulation by Extracellular Matrix Components and Growth Factors pp. 57-70
Authors: M. Bodo, T. Baroni and A. Tabilio
Abstract: 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-â1
(TGFâ1), 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 TGFâ 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.