Abstract
Even though the production of orthochromatic erythroblasts can be scaled up to fulfill clinical requirements, enucleation remains one of the critical rate-limiting steps in the production of transfusable red blood cells. Mammalian erythrocytes extrude their nucleus prior to entering circulation, likely to impart flexibility and improve the ability to traverse through capillaries that are half the size of erythrocytes. Recently, there have been many advances in our understanding of the mechanisms underlying mammalian erythrocyte enucleation. This review summarizes these advances, discusses the possible future directions in the field, and evaluates the prospects for improved ex vivo production of red blood cells.
Highlights
IntroductionEven though developed countries by and large have sufficient supplies of transfusable blood, an increase in the incidence of complications from allogenic immune reactions provides impetus to search for alternatives that are less immunogenic [1,2,3]
Blood transfusions are a common practice to treat severe anemia and shock
Elegant studies with murine primary erythroblasts have demonstrated that Rac1 and Rac2 function through mDia2 to contribute to actin accumulation in the constriction zone [36]. While these findings provide strong evidence to support a role for the actin cytoskeleton in erythroblast maturation, it is unclear regarding the specific role actin is playing in enucleation, including whether it interacts with nonmuscle myosin II to form a contractile actin ring similar to cytokinesis (Figure 1)
Summary
Even though developed countries by and large have sufficient supplies of transfusable blood, an increase in the incidence of complications from allogenic immune reactions provides impetus to search for alternatives that are less immunogenic [1,2,3]. CD34+ cells from umbilical cord blood, adult hematopoietic stem/progenitor cells, peripheral blood CD34+ cells, or human-induced pluripotent stem cells (iPS cells) can all be used as source for synthesizing RBCs [5]. In all these systems, the efficiency of enucleation is low. This review will summarize the current mechanistic understanding of enucleation, propose a new model, and discuss future research directions
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