Erythropoiesis is a vital process governed through various factors. There is extreme unavailability of suitable donor due to rare phenotypic blood groups and other related complications like hemoglobinopathies, polytransfusion patients, and polyimmunization. Looking at the worldwide scarcity of blood, especially in low income countries and the battlefield, mimicking erythropoiesis using ex vivo methods can provide an efficient answer to various problems associated with present donor derived blood supply system. Fortunately, there are many ex vivo erythropoiesis methodologies being developed by various research groups using stem cells as the major source material for large scale blood production. Most of these ex vivo protocols use a cocktail of similar growth factors under overlapping growth conditions. Erythropoietin (EPO) is a key regulator in most ex vivo protocols along with other growth factors such as SCF, IL-3, IGF-1, and Flt-3. Now transfusable units of blood can be produced by using these protocols with their set of own limitations. The present paper focuses on the molecular mechanism and significance of various growth factors in these protocols that shall remain helpful for large scale production. 1. Introduction According to a report by the World Health Organization (WHO), blood donation rate in high-income countries is 39.2 donations per 1000 population, whereas it is just 12.6 donations in middle-income and 4.0 donations in low-income countries out of which more than 50% of blood is being supplied by either family/replacement or paid donors. 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]. While differing in initial material and methodology used by different research groups, they all converse at a single point in using EPO as a key regulator in the ex vivo RBC generation measures. In general, all the methods described so far mimic the marrow microenvironment through the application of cytokines and/or coculture on stromal cells, coupled with substantial amplification of stem cells with 100% terminal differentiation into fully mature, functional RBCs [2]. Neildez-Nguyen et al., 2002, in their studies demonstrated a method to amplify/expand hematopoietic
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