Growth Factors

Hematopoietic homeostasis is tightly controlled by a group of hematopoietic cytokines. Each cytokine performs unique and/or multiple actions mediated by receptors whose cytoplasmic domains contain specialized regions initiating their various responses, including survival, proliferation, apoptosis, differentiation commitment, maturation, and functional activation. Cytokines are protein molecules and, when regulating cell growth, they are also termed growth factors. Individual cytokines can be lineage specific or can regulate cells in multiple lineages; for some cell types, such as hematopoietic stem cells (HSCs), progenitors, and precursors, the simultaneous action of multiple factors and cytokines is required for proliferative responses. These signals also affect the functions of mature cells and are involved in boosting the production of leukocytes in response to infection, red blood cells in response to anemia, and platelets in response to thrombocytopenia. Cytokines or growth factors are released systemically into the bloodstream not only by organs (e.g., the kidneys release erythropoietin [EPO] and the liver produces thrombopoietin [TPO]), but also by other bone marrow cells, such as stromal cells (fibroblasts and endothelial cells), lymphocytes, and macrophages. Hematopoietic cytokines include colony-stimulating factors (CSFs), interleukins (ILs), monokines, chemokines, and interferons (IFNs). Signaling molecules can also act more locally—for example, as in the confines of the bone marrow. These molecules may also target cells at long range or just affect target cells nearby (paracrine)—for example, within a local niche. In some cases, paracrine signaling requires cell-to-cell contact. Finally, a cell may release signaling molecules that it can in turn detect to affect its own behavior (autocrine signaling).