| The shortage of blood supply and the risk of transfusion-related infectious diseases make the blood transfusion facing serious challenge. Primary research goal of transfusion medicine is to find more secure and adequate blood sources. As the sustained development of stem cell technology, we may induce stem cells to red blood cells in vitro. And the stem cell derived red blood cells can be used as a blood substitute. Under the current technical conditions, ex-vivo production of fully matured red blood cell products faces a lot of difficulties. However, stem cell-derived erythroid progenitor cell (EPC) products also can be used as an alternative source for blood cells in some occasions. In the present study, we first induced the cord blood-derived hematopoietic stem/progenitor cells (HSPC) into erythroid progenitor cells in vitro. And then, we used a small molecule compounds to optimizing the induced amplification system. Finally, we tried to use the bioreactor to produce the EPC products in a large scale. This study established a serum-free system to efficiently induce the cord blood HSPC to EPC, and the efficiency was over90%. The in vitro cultured EPC were characterized by a series of methods. And the cellular dynamics of the erythroid differentiation was also analyzed. To further optimize the induction-amplification system, and to achieve large-scale amplification of stem cell-derived EPC, we added a small molecule compounds Dimethyloxalylglycine (DMOG) to simulate the hypoxic microenvironment. The results showed that DMOG improved the induction and amplification efficiency of cultured EPC. After the establishment of the EPC induction system, we used the the WAVE bioreactor with Fed-batch culture model to produce the stem cell derived EPC at a large scale. Our present study provided an experimental basis for future production of available EPCs as an alternative blood sources.Figure:33; Table:5; Reference:96. |
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