Essay On Erythropoiesis

In contrast, just 34% of low- and middle-income countries have a provision of a national haemovigilance system which monitors and improves the safety of the transfusion process indicating that in such countries safe blood availability is a major concern [1].To overcome the shortage of blood, ex vivo production of mature human red blood cells (RBCs) from stem cells of diverse origins has been demonstrated by various research groups [2].Therefore, it can be assumed that ex vivo erythropoiesis can be carried out utilizing various sources, namely, embryonic stem cells (ESCs), induced pluripotent stem cells (i PSCs), and hematopoietic stem cells (HSCs), from various sources, for example, embryo, bone marrow, peripheral blood, or umbilical cord blood.

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We attempt to discuss the significance of these growth factors specifically involved in ex vivo expansion methods for efficient measure in ex vivo erythropoietic expansion.

Since erythropoietin has been developed as a central regulator of all the ex vivo RBCs production methods, more attention has been given to understand the various facets of its impact on the same.

Many groups have reported use of mononuclear cells directly enriched with specific growth factors to overcome this issue but a specific protocol is the need of the hour.

Till date most suitable method in terms of yield available for ex vivo erythropoiesis is presented by Giarratana et al.

In order to develop an optimal culturing procedure, a detailed knowledge of the growth factors and their significance along with mode of action shall be understood.

There have been a large number of publications available about the structure, function, and significance of various growth factors in the regular erythropoietic process.The same group in 2009 reported up to 95% of enucleation of in vitro generated RBCs by the addition of Poloxamer 188 as an RBC survival enhancer.This enhancer increases the stability of the RBC membrane and decreases the fragility [6].It acts primarily on colony forming unit erythroid (CFU-E) inducing the proliferation and maturation through the stages of proerythroblast followed by reticulocytes and finally mature erythrocytes [11].CFU-E remains the primary target cell in the bone marrow for EPO, but it acts synergistically with other growth factors, namely, SCF, GM-CSF, 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 [2, 12].These precursors finally differentiate into specific cell types.In order to utilize/exploit these growth factors to copy or mimic nature in terms of generation of clinical grade red blood cells, we need to understand their role and how these growth factors are regulated in vivo.As per their findings, sequential supply of specific combinations of cytokines in a stepwise manner helped them to obtain large scale ex vivo differentiated enucleated RBCs.In first step Flt3-L, SCF, and TPO stimulated proliferation of HSCs, which was then followed by SCF, EPO, and IGF-1 aiding in the proliferation of erythroid progenitors and finally terminal erythroid differentiation was promoted by EPO and IGF-1. 2005, described an ex vivo methodology for producing fully mature human RBCs from hematopoietic stem/progenitor cells by applying G-CSF, IL-3, SCF, and EPO [4]. demonstrated a method in which they cultured CD34 cells in a serum free medium supplemented with two cytokine sets SCF IL-3 EPO and SCF IL-3 EPO TPO Flt3 for one week, followed by coculture upon mesenchymal cells derived from cord blood for two weeks to generate an almost pure clinical grade [5].The major growth factors regulating in vivo erythropoiesis are granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin- (IL-) 3, stem cell factor (SCF), IL-1, IL-6, IL-4, IL-9, IL-11, insulin growth factor-1 (IGF-1), and erythropoietin (EPO) [9, 10].Erythropoietin plays a pivotal role during later stages of erythroid maturation (Table 1).


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