The Growth Response of Erythrocyte Production to Increased Dense Condition

Abstract 4812

Erythroid precursors proliferate, differentiate, and enucleate in the bone marrow niches called erythroblastic islands in contact with macrophages. However, the cell-to-cell communication between erythroblasts which are undergoing terminal maturation leading to enucleation is not well known. Moreover, the cell-to-cell interaction at a terminal erythroblast maturation stage was hardly detected in conventional suspension culture systems due to cell surface characteristics of electrostatic repulsion.

To elucidate the communication between late maturing erythroblasts, erythroid cells, which were derived from human CD34+ cells, were cultured at conventional or supra-optimal densities. Surprisingly, the final yields of red blood cells (RBCs) were significantly increased in supra-optimal culture density, even in the absence of feeder stromal cells and serum or plasma. Also observed were increases in the rates of cell survival, expansion, and enucleation. Contact between cells observed in these supra-optimal cultures was associated with increases in adhesion-related signaling proteins (150 kDa and 123 kDa), the latter of which was previously unknown to be involved in erythropoiesis. The cultured erythroid cells showed erythropoiesis specific markers such as CD71, GPA, GATA-1 and b-globin.

Therefore, we firstly elucidated that the erythroid cells which were in the final maturation step can communicate each other and affect their survival and maturation including enucleation without the help of macrophages. Also, the increased attachments between erythroid cells evoked adhesion-related signals. We anticipate that the culture of these cells at supra-optimal density may enhance in vitro RBC production for human transfusion.