The existing transfusion system is expensive to maintain and vulnerable to potentially major disruptions that could be caused by the emergence of novel pathogens or social upheaval. Historical analysis of emergency responses after major natural or man-made disasters suggests that short-term blood needs in such circumstances are relatively small and can be fulfilled by locally available supplies [5]. Rather, the most threatening scenarios involve long-term disruption of the supply chain caused, for instance, by a major pandemic that would decrease the ability of the population to donate blood for an extended period of time [6]. Generally, supply problems and transient shortages are expected to worsen over the next 20 to 30 years because of current demographic trends in the Western world, with an increasing proportion of older people needing transfusion therapy and much smaller proportion of younger donors
Methods to immortalize hematopoietic cells with erythroid
potential have been developed in chicken and mouse over the
last 20 years. These extensive studies have shown that immortalization of erythroblasts can be achieved by manipulating the
expression of transcription factors, tumor suppressors, and nuclear receptors. In addition to the factors mentioned above, vErb-a (THRA), v-Erb-b, and Raf, as well as several other genes,
have been shown to have the potential to contribute to immortalization of erythroid precursors [32–36]. Some of the cell lines
created with these factors have retained the capacity to differentiate and enucleate.
These animal studies provide a strong theoretical basis for
the engineering of human erythroid cell lines that could be developed into highly scalable precursors for cRBC production. Importantly, this approach might be safe because cRBCs are not
oncogenic since they are enucleated and remain fully functional
after irradiation. The use of transformed cells to produce cRBCs
is therefore not a safety issue since contaminating precursors
could be eliminated. However, whether fully functional cRBCs
could be derived in large quantities from a transformed cell line
remains to be demonstrated. Hiroyama and colleagues have established a method to derive an immortalized hematopoietic line
from mouse embryonic stem (ES) cells without the use of transgenic oncogenes by simply growing ES cells in the presence of
stroma and hematopoietic cytokines [37, 38]. Three of the cell
lines produced retained the capacity to form enucleated RBCs
upon induction of differentiation [37, 38].
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