STUDYING THE EFFECT OF GROWTH FACTORS ON EXPANSION AND ERYTHROPOIETIC DIFFERENTIATION OF HEMATOPOIETIC STEM CELLS

Abstract

Red cell production in vertebrates is regulated by several cytokines and factors. The process of erythropoiesis is initiated from the primitive pluripotent stem cell giving rise to mature erythrocyte. This process involves various regulatory factors which induce commitment and further maturation of the cells involved in the red cell lineage. The major growth factors that are involved in Erythropoiesis are granulocyte colonystimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, interleukin (IL)-3, stem cell factor (SCF), IL-1, IL-6, IL-4, IL-9, IL-11, and insulin growth factor-1 (IGF1) and Erythropoietin (EPO) (Gregory et al. 1978). EPO comes in action during later stages of maturation of erythroid progenitor cells and primarily on colony-forming unit erythroid (CFU-E) to induce the proliferation and maturation of these cells through the stages of proerythroblast followed by reticulocytes and finally mature erythrocytes (Hillman and Henderson, 1969). CFU-E remains the primary target cell in the bone marrow for EPO but it acts synergistically with other growth factors viz. SCF, GMCSF, IL-3, IL-4, IL-9, and IGF-1 in order to regulate the maturation and proliferation starting from the stage of the burst-forming unit erythroid (BFU-E) followed by CFU-E to the proerythroblast stage of erythroid cell development (Douay et al., 2005; Yu et al., 2002). SCF, IL-1, IL-3, IL-6, and IL-11 stimulate pluripotent stem cell to differentiate into the CFU granulocyte, erythroid, monocyte, megakaryocyte (GEMM) and the myeloid stem cell. The CFU-GEMM then differentiates into specific CFU for erythroid, granulocytes, monocytes, macrophages, eosinophils, and megakaryocytes cell precursors in the presence of GM-CSF and IL3. These precursors finally differentiate into specific cell types. Besides the role of erythropoiesis EPO also inhibits apoptosis to decrease the rate of cell death in erythroid progenitor cells in the bone marrow and neural cells (Motoyoshi 1992). IL3 encodes an important growth factor/cytokine which supports the proliferation of a broad range of hematopoietic stem cell types and involved in a variety of other cell activities such as cell growth, differentiation and apoptosis. Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte- colony-stimulating factor (G-CSF) are important growth factors which have established roles in hematopoiesis and have an established role as growth factors in clinical practice. G-CSF and GM-CSF regulate myeloid cell production, differentiation and activation (Matthias et al., 1997).