Regulation of hemopoiesis by bone marrow stromal cells and their products.

Hemopoietic precursors can be identified in a number of tissues, but the bone marrow is the only site in normal adult mammals in which myelopoiesis, erythropoiesis, and lymphopoiesis proceed simultaneously (1). When intrave ' nous injection of hemopoietic precursors occurs as in experimental or clinical bone marrow transplantation, long-term hemo­ poiesis still establishes only in the bone marrow. Local tissue influences critical for hemopoiesis thus appear to operate primarily in the medullary cavity (2). Such observations have led to considerable interest in understand­ ing the nature of these influences. A cellular basis for these tissue-specific effects evolved from morphologic studies that demonstrated a close association between blood cells and fixed tissue elements, collectively referred to as stromal cells (3-5). The ability to grow nonhemopoietic, connective tissue cells of marrow origin in vitro and the demonstration that these supported hemopoiesis upon transplantation to ectopic sites in vivo strengthened this premise (6, 7). The application of modern experimental techniques to problems in stromal cell biology has begun to define the mech­ anisms by which stromal cells mediate their effects. One major advance in the last decade has been the development of cell culture techniques that make it possible to grow selected stromal cells, to study their hemo­ poietic support capabilities, and to identify and clone genes that encode novel, stromal cell--derived growth and differentiation factors (8, 9). Stro-