Abstract
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 usingex vivomethods can provide an efficient answer to various problems associated with present donor derived blood supply system. Fortunately, there are manyex vivoerythropoiesis methodologies being developed by various research groups using stem cells as the major source material for large scale blood production. Most of theseex vivoprotocols use a cocktail of similar growth factors under overlapping growth conditions. Erythropoietin (EPO) is a key regulator in mostex vivoprotocols 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.
Highlights
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
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
Summary
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. Human nucleated erythroid cells produced by this method when injected into nonobese diabetic, severe combined immunodeficient (NOD/SCID) mice showed proliferation and terminal differentiated into mature enucleated red blood cells (RBCs) [3]. 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 followed by SCF, EPO, and IGF-1 aiding in the proliferation of erythroid. If we compare ex vivo with in vivo erythropoiesis, it is regulated by several cytokines and factors
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