Abstract
BackgroundThe supply of transfusable red blood cells (RBCs) is not sufficient in many countries. If erythroid cell lines able to produce transfusable RBCs in vitro were established, they would be valuable resources. However, such cell lines have not been established. To evaluate the feasibility of establishing useful erythroid cell lines, we attempted to establish such cell lines from mouse embryonic stem (ES) cells.Methodology/Principal FindingsWe developed a robust method to obtain differentiated cell lines following the induction of hematopoietic differentiation of mouse ES cells and established five independent hematopoietic cell lines using the method. Three of these lines exhibited characteristics of erythroid cells. Although their precise characteristics varied, each of these lines could differentiate in vitro into more mature erythroid cells, including enucleated RBCs. Following transplantation of these erythroid cells into mice suffering from acute anemia, the cells proliferated transiently, subsequently differentiated into functional RBCs, and significantly ameliorated the acute anemia. In addition, we did not observe formation of any tumors following transplantation of these cells.Conclusion/SignificanceTo the best of our knowledge, this is the first report to show the feasibility of establishing erythroid cell lines able to produce mature RBCs. Considering the number of human ES cell lines that have been established so far, the intensive testing of a number of these lines for erythroid potential may allow the establishment of human erythroid cell lines similar to the mouse erythroid cell lines described here. In addition, our results strongly suggest the possibility of establishing useful cell lines committed to specific lineages other than hematopoietic progenitors from human ES cells.
Highlights
red blood cells (RBCs) transfusion was the first established transplantation procedure in clinical history, and is a common and indispensable clinical procedure
We cannot precisely describe the exact mechanism underlying the establishment of differentiated cell lines from embryonic stem (ES) cells
Given that differentiation strategies developed for mouse ES cells can differ from methods applied to human ES cells in many cases [33], the method we developed here may not be applied to human ES cells directly and some modifications may be necessary
Summary
RBC transfusion was the first established transplantation procedure in clinical history, and is a common and indispensable clinical procedure. If human erythroid progenitor cell lines were established that could produce transfusable and functional RBCs efficiently, they would represent a much more useful resource to produce RBCs than ES cell lines. If erythroid cell lines able to produce transfusable RBCs in vitro were established, they would be valuable resources. Such cell lines have not been established. We developed a robust method to obtain differentiated cell lines following the induction of hematopoietic differentiation of mouse ES cells and established five independent hematopoietic cell lines using the method. Three of these lines exhibited characteristics of erythroid cells. Our results strongly suggest the possibility of establishing useful cell lines committed to specific lineages other than hematopoietic progenitors from human ES cells
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