COMMUNICATION BETWEEN STEM-CELLS AND HEMATOPOIETIC ENVIRONMENT - EXPERIMENTAL-DATA AND MODELS OF INTERACTION

The aim of this review is to analyze the different ways by which stem cells and microenvironmental cells may interact. Stem cells are defined as immature cells that ensure the continuous renewal of blood cells. This small set of marrow cells comprises different kinds of cells, differing by their degree of maturity, their commitment, self-renewal ability and repopulating capacity. Microenvironmental cells are fixed marrow cells involved in stem cell survival, proliferation and differentiation. In vivo studies on the distribution within spleen or marrow, of stem cells injected to lethally irradiated mice, have suggested that cells of the microenvironment play a significant role in stem cell proliferation and differentiation. This role has been demonstrated using an in vitro model, i.e. the long-term marrow cultures as described in 1976 by M. Dexter. Analysis of stem cell maintenance in this culture system has made it possible to define the different means by which stromal cells and macrophages (the microenvironmental cells) may control stem cell behavior. Different molecules play a critical role : cytokines (growth factors and inhibitors), adhesion molecules (cell adhesion molecules and molecules belonging to the extracellular matrix) and eventually small peptides. It appears nowadays possible to materially represent the hemopoietic niche, whose existence was postulated by R. Schofield 10 years ago for theoretical reasons related to the the physiology of stem cells.