Abstract
Transfusion of red blood cells (RBCs) is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.
Highlights
The transfusion of red blood cells (RBCs) is a standard clinical therapy
human iPS cell lines (HiPS)-TAL1 cells showed a significant improvement in the efficiency of induction of hematopoietic cells when grown on OP9 feeder cells in the presence of insulin-like growth factor-II (IGF-II) and vascular endothelial growth factor (VEGF) (Figure 2)
Long-term cultures of HiPS-TAL1 cells were initiated on OP9 cells in the presence of stem cell factor (SCF), erythropoietin (EPO) and thrombopoietin (TPO)
Summary
The supply of RBCs for transfusion is dependent on donation of blood by large numbers of volunteers. The logical step was to create immortalized human erythroid progenitor cell lines that could provide a convenient and reliable ex vivo source for RBC production. These cell lines could be of value for a range of basic science investigations, for example, into erythroid differentiation and enucleation. The present study shows the feasibility of establishing immortalized human erythroid progenitor cell lines and demonstrates that enucleated RBCs can be induced to differentiate in these cell lines
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