[Progress and challenges in cell culture-based red blood cell production]

In vitro production of red blood cells (RBCs) using cell culture techniques has progressed substantially since the early 2000s and has a broad range of promising applications in transfusion medicine, diagnostics, drug discovery, and basic research. This review summarizes recent advances in RBC production technologies using three major cell sources: hematopoietic stem/progenitor cells, pluripotent stem cells (ES and iPS cells), and immortalized erythroid progenitor cell lines. Recent improvements in differentiation protocols and culture conditions have markedly increased cell expansion and enucleation efficiency. Moreover, cultured RBCs produced from these cell sources exhibit functional properties, including oxygen-carrying capacity and deformability, comparable to those of native reticulocytes. Despite these advances, major challenges remain for clinical translation, particularly in the development of transfusable blood products. The most critical challenge is to establish cost-effective, high-density, and scalable manufacturing systems capable of supplying large quantities of RBCs. Future technological innovations, such as advanced high-density culture platforms and further optimization of culture media, will be essential for practical and economically viable production of cultured RBCs for clinical applications.