Cell sources for large‐scale manufacture of red blood cells

Abstract

Owing to the high demand for blood production to replace donated blood, there have been many developments in the production methods of red blood cells (RBCs) in the past decades. Although cord blood or adult haematopoietic stem cells were shown to mature into functional reticulocytes in vitro, their limited proliferative capacity led to the development of new strategies that use pluripotent stem cells or cell lines that have been immortalized using gene modification techniques. This research highlights embryonic stem cells, induced pluripotent stem cells and immortalized cell lines as possible sources of RBCs. Despite the low enucleation efficiency of erythroblasts derived from these pluripotent stem cells, recent studies have shown the possibility of an increased yield of final enucleated red cell products. In addition, primary erythroid early progenitor cells could be used as a cell source by culture conditioning or the exogenous overexpression of adequate genes for self‐renewal and proliferation. The strategy of directly establishing immortalized erythroid progenitor cell lines is suitable for the manufacture of RBCs, since these cell lines are easy to maintain and mature rapidly. In this review, different approaches for the manufacture of erythrocytes, using more expandable precursor sources, are discussed.