| Popis: |
The present paper reports the various obstacles cleared during the past decade with the view of generating red blood cells in vitro from various sources of stem cells, for transfusion purposes. We also consider the next developments to be performed for achieving this goal. Starting from the natural source, the haematopoietic stem cells, the major advance resides in the establishment of the proof of principle for transfusion in human, by showing a normal life span of cultured Red blood cells compared to their native counterpart. The best available source of highly proliferative adult stem cells is cord blood, with the capacity of generating the equivalent of 100 units of packed RBC from one average unit. It is, however, a limited source in terms of haematopoietic stem cells and remains dependent on donations as observed from conventional blood supply. Critical advances have allowed the in vitro production of functional RBC from pluripotent human stem cells, embryonic and induced pluripotent stem cells, in the past 5 years. Because induced pluripotent stem cells (iPS) can proliferate indefinitely and be selected for a phenotype of interest, they appear the most favourable source of stem cells. Proof of concept of the generation of RBC from iPS has been made, but still needs to be optimized. We also discuss the key points that remain to be resolved to achieve an application for clinical transfusion. Several crucial points remain to be resolved notably to ensure the safety of iPS of clinical grade, the optimization of the erythrocyte differentiation and cellular amplification, and finally, the definition of GMP conditions for industrial production. |
